Trial Outcomes & Findings for Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL (NCT NCT01465334)

Last Updated: 2023-08-29

Results Overview

Induction ORR is the percentage of participants achieving a minimum of partial response (PR) over induction treatment based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. PR is a 50% or greater decrease of measured size of lymphadenopathy, hepatomegaly, splenomegaly as well as blood lymphocytes (over baseline), marrow infiltrate or B-lymphoid nodules and a 50% or greater increase from baseline in platelet count (or level \>100,000/micro liter), hemoglobin (or level \>11 grams/deciliter), neutrophils (or level \>1500/microliter).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.

Results posted on

2023-08-29

Participant Flow

Participants enrolled between December 2011 and November 2014.

Participant milestones

Participant milestones
Measure	Treatment Naive Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Overall Study STARTED	15	15
Overall Study Complete Part A Induction	12	15
Overall Study Complete Part B Induction	7	15
Overall Study Eligible for Allogeneic Transplant	9	9
Overall Study COMPLETED	13	9
Overall Study NOT COMPLETED	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Naive Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Overall Study Disease Progression	1	0
Overall Study Adverse Event	1	0
Overall Study Richter's transformation	0	3
Overall Study Refractory Disease	0	3

Baseline Characteristics

Ofatumumab With High Dose Methylprednisone Followed by Ofatumumab and Alemtuzumab in 17p CLL

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Total n=30 Participants Total of all reporting groups
Age, Continuous	64 years n=99 Participants	65 years n=107 Participants	65 years n=206 Participants
Sex: Female, Male Female	7 Participants n=99 Participants	3 Participants n=107 Participants	10 Participants n=206 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	12 Participants n=107 Participants	20 Participants n=206 Participants
Region of Enrollment United States	15 Participants n=99 Participants	15 Participants n=107 Participants	30 Participants n=206 Participants
Number of Prior Therapies 0	15 Participants n=99 Participants	0 Participants n=107 Participants	15 Participants n=206 Participants
Number of Prior Therapies 1	0 Participants n=99 Participants	6 Participants n=107 Participants	6 Participants n=206 Participants
Number of Prior Therapies 2	0 Participants n=99 Participants	4 Participants n=107 Participants	4 Participants n=206 Participants
Number of Prior Therapies 3	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Number of Prior Therapies 4	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Time from Diagnosis to First Therapy	6.9 months n=99 Participants	23 months n=107 Participants	12.4 months n=206 Participants
Time from Diagnosis to Start on Trial	6.8 months n=99 Participants	59.4 months n=107 Participants	27.6 months n=206 Participants
Whole Exome Sequencing-Mutations	22 mutations n=99 Participants	20 mutations n=107 Participants	21 mutations n=206 Participants
Whole Exome Sequencing-Copy Number Alterations	12.5 Events n=99 Participants	14 Events n=107 Participants	14 Events n=206 Participants

PRIMARY outcome

Timeframe: Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Induction Overall Response Rate (ORR)	73 percentage of participants Interval 49.0 to 90.0	60 percentage of participants Interval 36.0 to 81.0

SECONDARY outcome

Timeframe: Disease was evaluated after weeks 8 and 16 of Part A and at 12, 18 and 24 weeks during part B.

CR over induction treatment was based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. CR is absence of significant lymphadenopathy (nodes\<1.5 centimeters in long axis diameter), hepatomegaly, splenomegaly as well as blood lymphocytes\<4000/microliter, normocellular for age marrow with \<30% lymphocytes, no B-lymphoid nodules and platelet\>100,000/micro liter, hemoglobin\>11 grams/deciliter, neutrophils\>1500/microliter.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Number of Participants Achieving Induction Complete Response (CR)	0 participants	0 participants

SECONDARY outcome

Timeframe: Disease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

Overall ORR is the percentage of participants achieving a minimum of partial response (PR) over induction and maintenance treatment based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. PR is a 50% or greater decrease of measured size of lymphadenopathy, hepatomegaly, splenomegaly as well as blood lymphocytes (over baseline), marrow infiltrate or B-lymphoid nodules and a 50% or greater increase from baseline in platelet count (or level \>100,000/micro liter), hemoglobin (or level \>11 grams/deciliter), neutrophils (or level \>1500/microliter).

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Overall Objective Response Rate (ORR)	80 percentage of participants Interval 56.0 to 94.0	67 percentage of participants Interval 42.0 to 86.0

SECONDARY outcome

Timeframe: Disease was evaluated after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

CR overall (induction and maintenance treatment) was based on International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008). There are numerous diagnostic tests used for response evaluation including potentially CBC and differential count, marrow aspirate and biopsy, ultrasound of the abdomen, CT scans (chest, pelvis, abdomen) and physical examination. CR is absence of significant lymphadenopathy (nodes\<1.5 centimeters in long axis diameter), hepatomegaly, splenomegaly as well as blood lymphocytes\<4000/microliter, normocellular for age marrow with \<30% lymphocytes, no B-lymphoid nodules and platelet\>100,000/micro liter, hemoglobin\>11 grams/deciliter, neutrophils\>1500/microliter.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Number of Participants With Overall CR	2 participants	0 participants

SECONDARY outcome

Timeframe: MRD was assessed after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C.

Overall MRD negative rate is the percentage of participants classified as MRD negative by four color flow cytometry. The assay has a sensitivity of 1 in 10,000 leukocytes.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Overall MRD Negative Rate	80 percentage of participants Interval 56.0 to 94.0	53 percentage of participants Interval 30.0 to 76.0

SECONDARY outcome

Timeframe: Evaluated up to 36 cycles (approximately 2.75 years) of treatment (Parts A, B and C)

Percentage of participants eligible for allogeneic hematopoietic stem cell transplantation (alloHSCT) that are able and willing to proceed to alloHSCT.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Transplant Rate	43 percentage of participants Interval 21.0 to 67.0	43 percentage of participants Interval 21.0 to 67.0

SECONDARY outcome

Timeframe: Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks)

Participants ever experiencing a grade 1-3 hyperglycemia event based on CTCAEv4 with treatment attribution of possible, probably or definite as reported on case report forms were counted.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Number of Participants With Treatment-Related Grades 1-3 Hyperglycemia During Part A Induction	5 participants	6 participants

SECONDARY outcome

Timeframe: Disease was evaluated on treatment after weeks 8 and 16 of Part A, at 12, 18 and 24 weeks during part B and every 6 months on Part C as well as off-treatment every 3 months up to 5 years.

3-year PFS is the probability of participants remaining alive and progression-free at 3 years from study entry estimated using Kaplan-Meier methods. Disease progression (PD) per International Workshop on Chronic Lymphocytic Leukemia (IW-CLL) criteria (Hallek, et al 2008) is: the appearance of any new lesion (enlarged lymph node minimum \>1.5 centimeters); an increase by 50% in greatest determined diameter of any previous site; an increase in the previously noted enlargement of the liver or spleen by 50% or more or the de novo appearance of hepatomegaly, splenomegaly; a 50% increase of blood lymphocytes (over baseline with level at least 5,000/microliter); occurrence of cytopenia secondary to CLL at least 3 months post treatment including a 50% or greater decrease from baseline in platelet count (or level \<100,000/microliter) or a hemoglobin decrease of \>2 grams/deciliter (or level \<10 grams/deciliter); and transformation to a more aggressive histology.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
3-Year Progression-Free Survival (PFS) Probability	53 percentage probability Interval 25.0 to 74.0	25 percentage probability Interval 7.0 to 49.0

SECONDARY outcome

Timeframe: Median survival follow-up was 45 months (range 31-58 months) in this study cohort.

3-year OS is the probability of participants remaining alive at 3 years from study entry estimated using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
3-year Overall Survival (OS) Probability	66 percentage probability Interval 36.0 to 84.0	53 percentage probability Interval 26.0 to 74.0

SECONDARY outcome

Timeframe: Evaluated up to 4 cycles/16 weeks.

Participants counted as completing Part A with either 2 or 4 cycles of treatment per protocol.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Number of Participants Completing Part A Treatment	12 participants	15 participants

SECONDARY outcome

Timeframe: Evaluated after 2 cycles/8 weeks of Part A therapy.

Participants counted if only completed 2 cycles of Part A treatment per protocol.

Outcome measures

Outcome measures
Measure	Treatment Naive n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 Participants Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy as follows (cycle duration=28 days): Induction Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: cycle 1 - 300 mg intravenously (IV) Day 1 then 1000 mg IV Days 8, 15, 22; cycles 2-4 - 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants with nodal complete response at cycle 2 re-staging then discontinued Part A therapy. Induction Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants with at least stable disease could continue continue to Part C or, if eligible, proceed to allogeneic stem cell transplant (SCT) off study. Maintenance Part C: Ofatumumab + Alemtuzumab up to 26 cycles Ofatumumab: 1000 mg IV Day 1 every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Number of Participants Completing Only 2 Cycles of Part A Treatment	0 participants	0 participants

Adverse Events

Treatment Naive

Serious events: 11 serious events

Other events: 15 other events

Deaths: 7 deaths

Relapsed/Refractory

Serious events: 9 serious events

Other events: 14 other events

Deaths: 6 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Naive n=15 participants at risk Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy. (cycle duration=28 days) Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants who have not experienced a clinical complete response with no residual detectable disease after Part A will continue on to Part B. Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants who have experienced at least stable disease in Parts A and B can continue on to Part C. Participants who are eligible may instead proceed to stem cell transplantation after Parts A and B. Part C: Maintenance with Ofatumumab + Alemtuzumab up to 2 years Ofatumumab: 1000 mg IV every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28	Relapsed/Refractory n=15 participants at risk Participants were assigned to 1 of 2 groups based on prior treatment status. Both groups received the same therapy. (cycle duration=28 days) Part A: Ofatumumab + HDMP 2-4 cycles Ofatumumab: 1000 mg IV Days 1, 8, 15, 22 High-Dose Methylprednisolone (HDMP): 1000 mg/m2 IV Days 1-3 Participants who have not experienced a clinical complete response with no residual detectable disease after Part A will continue on to Part B. Part B: Ofatumumab + Alemtuzumab 1-6 cycles Ofatumumab: 1000 mg IV Day 1 Alemtuzumab: 30 mg subcutaneously Days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24 and 26 Participants who have experienced at least stable disease in Parts A and B can continue on to Part C. Participants who are eligible may instead proceed to stem cell transplantation after Parts A and B. Part C: Maintenance with Ofatumumab + Alemtuzumab up to 2 years Ofatumumab: 1000 mg IV every other cycle Alemtuzumab: 30 mg subcutaneously Days 14, 28
Blood and lymphatic system disorders Anemia	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Blood and lymphatic system disorders Febrile neutropenia	20.0% 3/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Investigations Growth hormone abnormal	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	0.00% 0/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Metabolism and nutrition disorders Hyperglycemia	20.0% 3/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	20.0% 3/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
General disorders Infusion related reaction	13.3% 2/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	0.00% 0/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Investigations Lymphocyte count decreased	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	13.3% 2/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Investigations Lymphocyte count increased	0.00% 0/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Musculoskeletal and connective tissue disorders Myalgia	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	0.00% 0/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Investigations Neutrophil count decreased	40.0% 6/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	46.7% 7/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Investigations Platelet count decreased	13.3% 2/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment related secondary malignancy	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	0.00% 0/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Skin and subcutaneous tissue disorders Urticaria	6.7% 1/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	0.00% 0/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.
Investigations White blood cell decreased	26.7% 4/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.	33.3% 5/15 • Adverse Events (AEs) were collected weekly during cycle 1 Part A and then every other week for the duration of Part A (up to 16 weeks); every cycle for the duration of Part B (up to 24 weeks); and every 56 days for the duration of Part C (up to 104 weeks). AEs in summary were collected up to 144 weeks of treatment plus 30 days. Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. Grades 1-2 AEs were not required reporting per protocol; all AEs collected were included in the calculation. No further data is available to specify classification of system organ class "Other" per CTCAEv4 criteria beyond the general term.

Other adverse events

Additional Information

Jennifer R. Brown, MD, PhD

Dana-Farber Cancer Institute

Phone: (617) 632-3316

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place