Trial Outcomes & Findings for Allo Non-Myeloablative SCT Utilizing Mis-Matched Family Member Stem Cells Purged Using Campath (NCT NCT00580034)
NCT ID: NCT00580034
Last Updated: 2014-06-03
Results Overview
Acute graft versus host disease (GVHD) was graded according to the consensus criteria and common terminology criteria (CTC) v3.0 was used for all other toxicities. Recognizing that acute GVHD pathology in the non-ablative 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.
COMPLETED
PHASE2
176 participants
1 year
2014-06-03
Participant Flow
Recruitment began in February, 2003 and ended in February, 2008. Recruitment took place at Duke and Florida hospitals in the Bone Marrow Transplant clinics during time of clinical appointments in a private location.
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. Prior to treatment, disease progression and insurance denial led to removal from the study.
Participant milestones
| Measure |
Campath Purged Non-myeloablative ASCT
Campath Purged Non-myeloablative allogeneic 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) 10-16 mcg/kg/d subcutaneously(dose will be rounded to the nearest whole vial size and may be divided into bid dosing). 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.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.
|
Donor Apheresis
Donor must be a sibling, half sibling, parent, child or first cousin familial relationship and 3-5/6 Human Leukocyte Antigen matched related to subject. They must not have any medical condition which would make apheresis and G-CSF administration more than a minimal risk, and should have the following:
1. Adequate cardiac function by history and physical examination
2. bilirubin and hepatic transaminases \< 2.5 x upper limit of normal
3. normal hematologic parameters Females should have a negative serum pregnancy test.
|
|---|---|---|
|
Overall Study
STARTED
|
88
|
88
|
|
Overall Study
COMPLETED
|
78
|
88
|
|
Overall Study
NOT COMPLETED
|
10
|
0
|
Reasons for withdrawal
| Measure |
Campath Purged Non-myeloablative ASCT
Campath Purged Non-myeloablative allogeneic 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) 10-16 mcg/kg/d subcutaneously(dose will be rounded to the nearest whole vial size and may be divided into bid dosing). 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.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.
|
Donor Apheresis
Donor must be a sibling, half sibling, parent, child or first cousin familial relationship and 3-5/6 Human Leukocyte Antigen matched related to subject. They must not have any medical condition which would make apheresis and G-CSF administration more than a minimal risk, and should have the following:
1. Adequate cardiac function by history and physical examination
2. bilirubin and hepatic transaminases \< 2.5 x upper limit of normal
3. normal hematologic parameters Females should have a negative serum pregnancy test.
|
|---|---|---|
|
Overall Study
Toxicity
|
10
|
0
|
Baseline Characteristics
Allo Non-Myeloablative SCT Utilizing Mis-Matched Family Member Stem Cells Purged Using Campath
Baseline characteristics by cohort
| Measure |
Campath Purged Non-myeloablative ASCT
n=88 Participants
Campath Purged Non-myeloablative ASCT in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors
Donor: Will receive granulocyte colony stimulating factor (G-CSF) 10-16 mcg/kg/d subcutaneously (dose will be rounded to the nearest whole vial size and may be divided into twice daily dosing). Granulocyte macrophage colony stimulating factor (GM-CSF) 15 mcg/kg/d sc 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.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
80 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
8 Participants
n=5 Participants
|
|
Age, Continuous
|
49 years
STANDARD_DEVIATION 24 • n=5 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
54 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
88 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: Cohort of subjects on the study 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 considered evaluable from the day of first donor lymphocyte (DLI) infusion. Results are not exclusive.
Acute graft versus host disease (GVHD) was graded according to the consensus criteria and common terminology criteria (CTC) v3.0 was used for all other toxicities. Recognizing that acute GVHD pathology in the non-ablative 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.
Outcome measures
| Measure |
Campath Purged Non-myeloablative ASCT
n=86 Participants
Campath Purged Non-myeloablative allogeneic 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) 10-16 mcg/kg/d subcutaneously (dose will be rounded to the nearest whole vial size and may be divided into twice daily dosing). 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.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.
|
|---|---|
|
Toxicity
Multi-organ failure
|
1 participants
|
|
Toxicity
Hepatic Veno-Occlusive Disease
|
1 participants
|
|
Toxicity
Post-transplant lymphoproliferative disorder
|
2 participants
|
|
Toxicity
Acute Graft versus Host Disease (aGvHD)
|
5 participants
|
|
Toxicity
Sepsis
|
3 participants
|
|
Toxicity
Infection
|
10 participants
|
|
Toxicity
Graft Failure
|
17 participants
|
|
Toxicity
Cardiac
|
3 participants
|
|
Toxicity
Acute respiratory distress syndrome
|
2 participants
|
PRIMARY outcome
Timeframe: 8 yearsPopulation: Subjects who completed CAMPATH regimen + 45 days, until disease progression, or death.
Estimate toxicity and overall survival rates in subjects treated with a non-myeloablative preparative regimen followed by matched related allogeneic stem cells for allogeneic transplantation.
Outcome measures
| Measure |
Campath Purged Non-myeloablative ASCT
n=78 Participants
Campath Purged Non-myeloablative allogeneic 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) 10-16 mcg/kg/d subcutaneously (dose will be rounded to the nearest whole vial size and may be divided into twice daily dosing). 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.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.
|
|---|---|
|
Overall Survival (OS)
|
20 months
Interval 0.03 to 101.0
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: 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: a) absence of pathologic lymphadenopathy by physical and radiographic exam b) absence of constitutional symptoms due to disease c) Polymorphonuclear leukocyte count \>1,500/uL; platelet count \>50,000/uL; and hemoglobin \>10.0 g/dL d) 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. e) 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
| Measure |
Campath Purged Non-myeloablative ASCT
n=88 Participants
Campath Purged Non-myeloablative allogeneic 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) 10-16 mcg/kg/d subcutaneously (dose will be rounded to the nearest whole vial size and may be divided into twice daily dosing). 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.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.
|
|---|---|
|
Response
Complete Response
|
6 months
Interval 4.0 to 19.0
|
|
Response
Partial Response
|
4.5 months
Interval 3.0 to 6.0
|
Adverse Events
Campath Purged Non-myeloablative ASCT
Serious adverse events
| Measure |
Campath Purged Non-myeloablative ASCT
n=88 participants at risk
Campath Purged Non-myeloablative ASCT in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors
Donor: Will receive granulocyte colony stimulating factor (G-CSF) 10-16 mcg/kg/d subcutaneously (dose will be rounded to the nearest whole vial size and may be divided into twice daily dosing). Granulocyte macrophage colony stimulating factor (GM-CSF) 15 mcg/kg/d subcutaneously 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.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.
|
|---|---|
|
General disorders
Death
|
80.7%
71/88 • Number of events 71 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Blood and lymphatic system disorders
Hemorrhage
|
13.6%
12/88 • Number of events 13 • From the beginning of Campath regimen until 6 years after transplant.
|
Other adverse events
| Measure |
Campath Purged Non-myeloablative ASCT
n=88 participants at risk
Campath Purged Non-myeloablative ASCT in lymphoma, myeloma, or marrow failure: leukemia or myelodysplasia; and solid tumors
Donor: Will receive granulocyte colony stimulating factor (G-CSF) 10-16 mcg/kg/d subcutaneously (dose will be rounded to the nearest whole vial size and may be divided into twice daily dosing). Granulocyte macrophage colony stimulating factor (GM-CSF) 15 mcg/kg/d subcutaneously 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.
Patient Evaluation: Will occur 2-3 times per week by physical exam for toxicity through day 45.
|
|---|---|
|
Blood and lymphatic system disorders
Failure to Engraft
|
18.2%
16/88 • Number of events 17 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Blood and lymphatic system disorders
Cardiac Left Ventricular Function
|
6.8%
6/88 • Number of events 7 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Blood and lymphatic system disorders
Rash / desquamation
|
6.8%
6/88 • Number of events 6 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Blood and lymphatic system disorders
Diarrhea
|
10.2%
9/88 • Number of events 10 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Blood and lymphatic system disorders
Vomiting
|
5.7%
5/88 • Number of events 5 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
33.0%
29/88 • Number of events 36 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Infections and infestations
Infection - other
|
11.4%
10/88 • Number of events 10 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Infections and infestations
Infection - with grade 3 or 4 neutrophils
|
39.8%
35/88 • Number of events 65 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Infections and infestations
Infection - grade 1 or 2 neutrophils
|
13.6%
12/88 • Number of events 25 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Infections and infestations
Infection - without febrile neutropenia
|
34.1%
30/88 • Number of events 64 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Metabolism and nutrition disorders
Metabolic - Creatinine
|
8.0%
7/88 • Number of events 7 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Nervous system disorders
Seizure
|
6.8%
6/88 • Number of events 6 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.8%
6/88 • Number of events 8 • From the beginning of Campath regimen until 6 years after transplant.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
15.9%
14/88 • Number of events 15 • From the beginning of Campath regimen until 6 years after transplant.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place