Trial Outcomes & Findings for Lenalidomide + Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL) (NCT NCT01373229)
NCT ID: NCT01373229
Last Updated: 2018-02-05
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
21 participants
Primary outcome timeframe
4-16 months
Results posted on
2018-02-05
Participant Flow
Subjects were recruited from the CLL clinic at Duke Medical Center from January 2012 to December 2013.
21 subjects were consented to this study. Six (6) were screen failures; therefore, only 15 subjects began the treatment regimen which included a lenalidomide run-in phase. Three (3) subjects were unable to complete the run-in phase. Three (3) subjects died prior to completing stage 2, and so were not evaluable for DLT.
Participant milestones
| Measure |
Lenalidomide + Plerixafor+ Rituximab
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Overall Study
STARTED
|
15
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
Lenalidomide + Plerixafor+ Rituximab
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Overall Study
Death
|
3
|
|
Overall Study
Physician Decision
|
3
|
Baseline Characteristics
Lenalidomide + Plerixafor in Previously Treated Chronic Lymphocytic Leukemia (CLL)
Baseline characteristics by cohort
| Measure |
Lenalidomide + Plerixafor+ Rituximab
n=15 Participants
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 4-16 monthsOutcome measures
| Measure |
Lenalidomide + Plerixafor+ Rituximab
n=9 Participants
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Maximum Tolerated Dose
|
0.24 mg/kg
|
SECONDARY outcome
Timeframe: at the end of 4 months of combination treatment and at 2 months after completion of therapyPopulation: Three (3) subjects were unable to complete the run-in phase. Three (3) subjects died prior to completing stage 2, and three (3) subjects were unable to complete 4 cycles of combination therapy. Therefore, only 6 subjects were analyzed for response.
NCI 96 Response Criteria CR (Complete Response): Lymphadenopathy = none \> 1.5cm Hepatomegaly = none Splenomegaly = none Blood lymphocytes = \<4000 per microliter Marrow = normocellular, \<30% lymphocytes, no B-lymphoid nodules. Platelet count = \>100,000 per microliter Hemoglobin = \>11.0 grams per deciliter Neutrophils = \>1500 per microliter PR (Partial Response): Lymphadenopathy = Decrease \>/= 50% Hepatomegaly = Decrease \>/= 50% Splenomegaly = Decrease \>/= 50% Blood lymphocytes = Decrease \>/= 50% from baseline Marrow = 50% reduction in marrow infiltrate or B-lymphoid nodules. Platelet count = \>100,000 per microliter or increase \>/= 50% over baseline Hemoglobin = \>11.0 grams per deciliter or increase \>/= 50% over baseline Neutrophils = \>1500 per microliter or increase \>/= 50% over baseline
Outcome measures
| Measure |
Lenalidomide + Plerixafor+ Rituximab
n=6 Participants
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Overall Response (Complete Response/Partial Response)
|
0 Participants
|
SECONDARY outcome
Timeframe: time from day 1 of treatment to disease progression, death, or 2 years, whichever comes firstPopulation: Subjects who experienced disease progression
Outcome measures
| Measure |
Lenalidomide + Plerixafor+ Rituximab
n=3 Participants
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Progression-free Survival (PFS)
|
11 months
Standard Deviation 1
|
SECONDARY outcome
Timeframe: the time from day 1 of treatment to death or 2 years, whichever comes firstPopulation: Subjects who died on study
Outcome measures
| Measure |
Lenalidomide + Plerixafor+ Rituximab
n=8 Participants
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Overall Survival (OS)
|
5.5 months
Standard Deviation 10
|
SECONDARY outcome
Timeframe: at the end of stage 1 (lenalidomide alone), at the end of stage 2 (4 months of combination), and at 2 months post-completion of therapyPopulation: Data were not collected and the Outcome will never be analyzed
Reduction in the severity of the following B symptoms will be assessed: fever ≥ 101F, chills, night sweats, and anorexia with weight loss.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 4 weeks prior to therapy and in the 4 weeks following the completion of therapyPopulation: Data were not collected and the Outcome will never be analyzed
The change in number of transfusions from pre- to post-treatment will be calculated and summarized across all patients by giving the minimum, the 25th, 50th (median) and the 75th percentile and the maximum.
Outcome measures
Outcome data not reported
Adverse Events
Lenalidomide + Plerixafor+ Rituximab
Serious events: 14 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lenalidomide + Plerixafor+ Rituximab
n=15 participants at risk
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
6.7%
1/15 • Number of events 1
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
13.3%
2/15 • Number of events 2
|
|
Blood and lymphatic system disorders
Hemolysis
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Death NOS
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Fever
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Infections and infestations - Other, specify
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Sepsis
|
13.3%
2/15 • Number of events 2
|
|
Investigations
Platelet count decreased
|
6.7%
1/15 • Number of events 1
|
|
Investigations
White blood cell decreased
|
6.7%
1/15 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Dysphasia
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
20.0%
3/15 • Number of events 3
|
|
Vascular disorders
Hypotension
|
6.7%
1/15 • Number of events 1
|
|
Vascular disorders
Thromboembolic event
|
6.7%
1/15 • Number of events 1
|
Other adverse events
| Measure |
Lenalidomide + Plerixafor+ Rituximab
n=15 participants at risk
1. Lenalidomide 5mg by mouth (PO) daily beginning cycle 1 day 1.
2. Stage 1: increase by 2.5mg every 7 days to a maximum dose of 10mg.
3. Stage 2: plerixafor will be added after 28 days of 10mg dose maintenance and white blood cell count (WBC) \<100.0 x 109 / L.
4. Dose cohorts of escalating subcutaneous (SC) thrice weekly plerixafor with continuous 10mg lenalidomide:
* Cohort 1: 0.24 mg/kg
* Cohort 2: 0.32 mg/kg
5. Stage 3: Rituximab 375mg/m2 will be added on day 1 of cycles 5-12, day 1 of combination therapy for subjects with PR.
6. Subjects will then continue single agent lenalidomide until disease progression.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
86.7%
13/15 • Number of events 14
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other, specify
|
6.7%
1/15 • Number of events 2
|
|
Blood and lymphatic system disorders
Lymph node pain
|
6.7%
1/15 • Number of events 1
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, specify
|
6.7%
1/15 • Number of events 1
|
|
Ear and labyrinth disorders
Hearing impaired
|
6.7%
1/15 • Number of events 1
|
|
Eye disorders
Blurred vision
|
6.7%
1/15 • Number of events 1
|
|
Eye disorders
Dry eye
|
6.7%
1/15 • Number of events 1
|
|
Eye disorders
Eye disorders - Other, specify
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Anal ulcer
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
20.0%
3/15 • Number of events 3
|
|
Gastrointestinal disorders
Diarrhea
|
26.7%
4/15 • Number of events 6
|
|
Gastrointestinal disorders
Dry mouth
|
20.0%
3/15 • Number of events 3
|
|
Gastrointestinal disorders
Dyspepsia
|
6.7%
1/15 • Number of events 2
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
20.0%
3/15 • Number of events 3
|
|
Gastrointestinal disorders
Nausea
|
33.3%
5/15 • Number of events 5
|
|
Gastrointestinal disorders
Stomach pain
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Chills
|
6.7%
1/15 • Number of events 1
|
|
General disorders
Edema limbs
|
33.3%
5/15 • Number of events 5
|
|
General disorders
Fatigue
|
60.0%
9/15 • Number of events 12
|
|
General disorders
Fever
|
20.0%
3/15 • Number of events 4
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
26.7%
4/15 • Number of events 5
|
|
General disorders
Pain
|
20.0%
3/15 • Number of events 3
|
|
Immune system disorders
Allergic reaction
|
6.7%
1/15 • Number of events 1
|
|
Immune system disorders
Cytokine release syndrome
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Infections and infestations - Other, specify
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Sinusitis
|
26.7%
4/15 • Number of events 4
|
|
Infections and infestations
Skin infection
|
6.7%
1/15 • Number of events 1
|
|
Investigations
Creatinine increased
|
13.3%
2/15 • Number of events 2
|
|
Investigations
Neutrophil count decreased
|
86.7%
13/15 • Number of events 27
|
|
Investigations
Platelet count decreased
|
73.3%
11/15 • Number of events 16
|
|
Investigations
Weight loss
|
13.3%
2/15 • Number of events 2
|
|
Metabolism and nutrition disorders
Anorexia
|
46.7%
7/15 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
13.3%
2/15 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
13.3%
2/15 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
6.7%
1/15 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
13.3%
2/15 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
6.7%
1/15 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Concentration impairment
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Dysgeusia
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Extrapyramidal disorder
|
6.7%
1/15 • Number of events 1
|
|
Nervous system disorders
Headache
|
13.3%
2/15 • Number of events 2
|
|
Nervous system disorders
Paresthesia
|
6.7%
1/15 • Number of events 2
|
|
Psychiatric disorders
Agitation
|
6.7%
1/15 • Number of events 1
|
|
Psychiatric disorders
Depression
|
6.7%
1/15 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
13.3%
2/15 • Number of events 2
|
|
Renal and urinary disorders
Urinary frequency
|
13.3%
2/15 • Number of events 4
|
|
Renal and urinary disorders
Urinary urgency
|
6.7%
1/15 • Number of events 1
|
|
Reproductive system and breast disorders
Reproductive system and breast disorders - Other, specify
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
46.7%
7/15 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
26.7%
4/15 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
Hoarseness
|
6.7%
1/15 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
33.3%
5/15 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
13.3%
2/15 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
6.7%
1/15 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
13.3%
2/15 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
20.0%
3/15 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
6.7%
1/15 • Number of events 2
|
|
Vascular disorders
Hot flashes
|
20.0%
3/15 • Number of events 3
|
|
Vascular disorders
Hypotension
|
6.7%
1/15 • Number of events 1
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place