Trial Outcomes & Findings for Allo Non-myeloablative SCT Utilizing Matched Family Member Stem Cells Purged Using Campath (NCT NCT00578942)

Last Updated: 2016-06-24

Results Overview

Acute graft versus host disease (GVHD) was graded according to the consensus criteria and NCI common terminology criteria for adverse events (CTCAE) v2.0 or 3.0 was used for all other toxicities. Recognizing that acute GVHD pathology in the nonablative and donor lymphocyte infusion (DLI) setting may occur late, we tabulated skin, gut and liver toxicity consistent with acute GVHD (aGVHD) at anytime in the year following the infusion as aGVHD. Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

48 participants

Primary outcome timeframe

1 year

Results posted on

2016-06-24

Participant Flow

This study was opened and first consent obtained on 9/11/2002 and was closed to accrual on 2/18/2008 as enrollment goal was met. Recruitment took place at Duke hospital in the Bone Marrow Transplant clinic during time of clinical appointments in a private location. Follow up for survival was discontinued in April 2013.

Prior to selecting a donor: donor and subjects had history and physical exam, labs and chest x-ray performed per program and FACT requirements. Female donors should have a negative pregnancy test. Subjects also had bone marrow aspirate/biopsy. Subjects were premedicated with Benadryl and acetaminophen.

Participant milestones

Participant milestones
Measure	Campath Purged Non-myeloablative ASCT Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Subject Evaluation will occur 2-3 times per week by physical exam for toxicity through day 45.
Overall Study STARTED	48
Overall Study COMPLETED	47
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Campath Purged Non-myeloablative ASCT Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Subject Evaluation will occur 2-3 times per week by physical exam for toxicity through day 45.
Overall Study Lost to Follow-up	1

Baseline Characteristics

Allo Non-myeloablative SCT Utilizing Matched Family Member Stem Cells Purged Using Campath

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Campath Purged Non-myeloablative ASCT n=48 Participants Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Patient Evaluation will occur 2-3 times per week by physical exam for toxicity through day 45.
Age, Categorical <=18 years	1 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=99 Participants
Age, Categorical >=65 years	6 Participants n=99 Participants
Sex: Female, Male Female	17 Participants n=99 Participants
Sex: Female, Male Male	31 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	6 Participants n=99 Participants
Race (NIH/OMB) White	42 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
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	48 participants n=99 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Cohort of subjects who received \>/=1 donor lymphocyte infusion (DLI). DLI doses thus ranged from 1×104 CD3+ cells/kg to 3.27 ×108 CD3+ cells/kg.Subjects were grouped into 4 categories within the range of cell doses delivered and were considered evaluable from the day of first donor lymphocyte (DLI) infusion. Results are not exclusive.

Outcome measures

Outcome measures
Measure	Campath Purged Non-myeloablative ASCT n=48 Participants Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors Donor will receive Granulocyte colony-stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily (dose will be rounded to the nearest whole vial size), Granulocyte-macrophage colony-stimulating factor (GM-CSF) 15 mcg/kg/d subcutaneous or similar growth factor for donor mobilization. Donors will receive at least 3-6 doses of daily growth factor until adequate cells are mobilized. Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Subject Evaluation will occur 2-3 times per week by physical exam for toxicity through day 45.
Toxicity acute Graft versus Host Disease	21 participants
Toxicity Death	25 participants

PRIMARY outcome

Timeframe: Up to 12 years; participants were followed for the duration of the study, an average of 8 years

Population: Subjects who completed CAMPATH regimen + 45 days, until disease progression, or death. One participant who was lost to follow-up after 14 months was not included. Participants were followed for the duration of the study, an average of 8 years.

Estimate overall survival rates in subjects treated with a non-myeloablative preparative regimen followed by matched related allogeneic stem cells for allogeneic transplantation.

Outcome measures

Outcome measures
Measure	Campath Purged Non-myeloablative ASCT n=47 Participants Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors Donor will receive Granulocyte colony-stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily (dose will be rounded to the nearest whole vial size), Granulocyte-macrophage colony-stimulating factor (GM-CSF) 15 mcg/kg/d subcutaneous or similar growth factor for donor mobilization. Donors will receive at least 3-6 doses of daily growth factor until adequate cells are mobilized. Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Subject Evaluation will occur 2-3 times per week by physical exam for toxicity through day 45.
Overall Survival (OS)	32 months alive post-infusion Interval 2.0 to 123.0

SECONDARY outcome

Timeframe: 1 year

Population: Cohort of subjects on the study who actually received \>/=1 donor lymphocyte infusion (DLI). DLI doses ranged from 1×104 CD3+ cells/kg to 3.27 ×108 CD3+ cells/kg. Subjects were considered for a second and third DLI 8 weeks apart if they did not have \>grade 2 toxicity from the initial DLI, donor availability, and insurance approved the infusion.

Response Assessment included physical exam and evaluation of peripheral blood and bone marrow. There's no widely accepted criteria for response other than complete response (CR). CR for malignant hematologic diseases is met if all the following are met for \>/= 1 month: 1. absence of pathologic lymphadenopathy by physical and radiographic exam 2. absence of constitutional symptoms due to disease 3. Polymorphonuclear leukocyte count \> 1,500/uL; platelet count \>50,000/uL; and hemoglobin \>10.0 g/dL 4. bone marrow aspirate/biopsy done after (a) through (c) have been met, \>/= 30% cellularity and an absence of abnormal lymphoid nodules or cells by flow cytometry, cytogenetics, etc. 5. molecular markers of disease must be negative by polymerase chain reaction, Fluorescence in situ hybridization, cytogenetics etc. CR for solid tumors requires complete resolution of disease on physical exam and radiographs. CR for marrow failure is normal white cell, platelet and hematocrit values.

Outcome measures

Outcome measures
Measure	Campath Purged Non-myeloablative ASCT n=48 Participants Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors Donor will receive Granulocyte colony-stimulating factor (G-CSF) 8 mcg/kg/d subcutaneously twice daily (dose will be rounded to the nearest whole vial size), Granulocyte-macrophage colony-stimulating factor (GM-CSF) 15 mcg/kg/d subcutaneous or similar growth factor for donor mobilization. Donors will receive at least 3-6 doses of daily growth factor until adequate cells are mobilized. Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Subject Evaluation will occur 2-3 times per week by physical exam for toxicity through day 45.
Response	18 participants

Adverse Events

Campath Purged Non-myeloablative ASCT

Serious events: 36 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Campath Purged Non-myeloablative ASCT n=48 participants at risk Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Subject Evaluation will occur 2-3 times per week by physical exam for toxicity through day 45.
General disorders Death	75.0% 36/48 • Number of events 36 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Blood and lymphatic system disorders Thrombotic microangiopathy	2.1% 1/48 • Number of events 1 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Vascular disorders Hemorrhage	10.4% 5/48 • Number of events 6 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.

Other adverse events

Other adverse events
Measure	Campath Purged Non-myeloablative ASCT n=48 participants at risk Campath Purged Non-myeloablative Allo Stem Cell Transplant (ASCT) in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors Preparative regimen: Begins on day -5 and consist of 4 days of daily fludarabine at 30 mg/m2/d infused over 30 minutes, cyclophosphamide 500 mg/m2/d infused over 1 hour, 5 days of Campath-1H at 20 mg/d in 250 ml of D5 normal saline or normal saline infused over 3 hours. Subject Evaluation will occur 2-3 times per week by physical exam for toxicity through day 45.
Immune system disorders Allergic reaction / hypersensitivity	4.2% 2/48 • Number of events 2 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Vascular disorders Hypotension	8.3% 4/48 • Number of events 4 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Gastrointestinal disorders Diarrhea	16.7% 8/48 • Number of events 9 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Gastrointestinal disorders Vomiting	8.3% 4/48 • Number of events 4 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Blood and lymphatic system disorders Febrile neutropenia	33.3% 16/48 • Number of events 21 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Investigations Creatinine	6.2% 3/48 • Number of events 4 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Nervous system disorders Neuropathy: motor	2.1% 1/48 • Number of events 2 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Nervous system disorders Neuropathy: sensory	2.1% 1/48 • Number of events 1 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Nervous system disorders Seizure	2.1% 1/48 • Number of events 1 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Respiratory, thoracic and mediastinal disorders Dyspnea	4.2% 2/48 • Number of events 2 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Respiratory, thoracic and mediastinal disorders Hypoxia	10.4% 5/48 • Number of events 6 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.2% 3/48 • Number of events 4 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Gastrointestinal disorders Failure to engraft	2.1% 1/48 • Number of events 1 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Cardiac disorders Ventricular arrhythmia	4.2% 2/48 • Number of events 2 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Cardiac disorders Cardiac Left Ventricular Function	4.2% 2/48 • Number of events 3 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Infections and infestations Infection with Grade 3 or 4 neutrophils	25.0% 12/48 • Number of events 16 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.
Infections and infestations Infection with normal ANC or Grade 1/2 neutrophils	10.4% 5/48 • Number of events 6 • Toxicities were formally recorded for all patients twice weekly for the first 100 days, at each follow up visit, and as needed intercurrently, up to 10 years NCI Common Terminology Criteria for Adverse Events version 3 was used to grade toxicities. The drug manufacturer, Berlex, required the reporting of all Serious Adverse Events associated with the study to Berlex Global Medical Safety Surveillance Group.

Additional Information

David Rizzieri, MD

Duke University Medical Center

Phone: 919-668-1040

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place