Trial Outcomes & Findings for A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies (NCT NCT01036009)
NCT ID: NCT01036009
Last Updated: 2016-06-23
Results Overview
Definition of relapse was \>5 % blasts in bone marrow
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
43 participants
Primary outcome timeframe
2 years post transplant.
Results posted on
2016-06-23
Participant Flow
5 eligible patients relapsed/died before assignment to a study arm
Participant milestones
| Measure |
Group I: Observation
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
26
|
|
Overall Study
COMPLETED
|
17
|
26
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies
Baseline characteristics by cohort
| Measure |
Group I: Observation
n=17 Participants
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
n=26 Participants
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
Total
n=43 Participants
Total of all reporting groups
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|---|---|---|---|
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Age, Continuous
|
10.12 years
STANDARD_DEVIATION 7.25 • n=5 Participants
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11.3 years
STANDARD_DEVIATION 6 • n=7 Participants
|
10.84 years
STANDARD_DEVIATION 6.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
26 participants
n=7 Participants
|
43 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 years post transplant.Definition of relapse was \>5 % blasts in bone marrow
Outcome measures
| Measure |
Group I: Observation
n=17 Participants
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
n=26 Participants
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
|
Relapse at 2 Years Post-transplant.
|
6 participants
|
4 participants
|
SECONDARY outcome
Timeframe: 2 years post transplantOutcome measures
| Measure |
Group I: Observation
n=17 Participants
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
n=26 Participants
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
|
2 Years Post-transplant Survival.
|
11 participants
|
21 participants
|
SECONDARY outcome
Timeframe: 2 years post transplantDefinition and diagnostic criteria of aGVHD according to: 1994 Consensus Conference on Acute GVHD Grading. Przepiorka D1, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. Bone Marrow Transplant. 1995 Jun;15(6):825-8. In this system, patients are divided into one of four grades (I-IV) depending on the degree, or stage, of involvement in three organs. The skin is staged with percent body surface involved, the liver is staged with degree of bilirubin elevation, and the gastrointestinal tract is staged with amount of diarrhea.
Outcome measures
| Measure |
Group I: Observation
n=17 Participants
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
n=26 Participants
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
|
The Incidence of Acute Graft Versus Host Disease (aGVHD).
|
11 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 2 years post transplantDiagnostic criteria of cGVHD from: Filipovich AH, Weisdorf D, Pavletic S et al. National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-host disease: I Diagnosis and Staging Working Group Report. Biology of Blood and Marrow Transplantation 2005;11:945-955. The diagnosis of chronic GVHD requires the following: 1\) Distinction from acute GVHD; 2) Presence of at least 1 diagnostic clinical sign of chronic GVHD or presence of at least 1 distinctive manifestation confirmed by pertinent biopsy or other relevant tests; 3) Exclusion of other possible diagnoses. Scoring of organ manifestations requires careful assessment of signs, symptoms, laboratory values, and other study results. A clinical scoring system (0-3) is used for evaluation of the involvement of individual organs and sites. Global assessment of severity (mild, moderate, or severe) is derived by combining organ- and site-specific scores.
Outcome measures
| Measure |
Group I: Observation
n=17 Participants
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
n=26 Participants
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
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The Incidence of Chronic GVHD (cGVHD).
|
6 participants
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2 participants
|
POST_HOC outcome
Timeframe: 24-36 months post-transplantPopulation: surviving patients in the intervention arm who had not relapsed as of 24 months were followed for an additional 12 months (until 3 years post-transplant)
The number of patients who relapsed after 2-year primary endpoint. To assess a potential for late relapse-rate in the intervention arm only, patients in the intervention arm were provided additional follow-up until 3-yrs post transplant. The criterion for relapse was \>5% blasts in bone marrow.
Outcome measures
| Measure |
Group I: Observation
n=21 Participants
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
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Late Relapses
|
4 participants
|
—
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POST_HOC outcome
Timeframe: 24-36 months post-transplantPopulation: intervention patients who relapsed after the 2 year primary study endpoint
Number of months post-transplant until late relapse, in intervention patients relapsing after the 2-year primary study endpoint. Relapse defined as \>5% blasts in bone marrow
Outcome measures
| Measure |
Group I: Observation
n=4 Participants
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
|
Time Until Late Relapse
|
32.025 months
Interval 25.0 to 36.32
|
—
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Adverse Events
Group I: Observation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Group II: Intervention
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group I: Observation
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
n=26 participants at risk
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
intervention-related-death
|
—
0/0 • 2 years
Due to the severity of illness in this patient population, this study collected and reported Adverse Events only if at least possibly related to study participation, and only in patients undergoing study intervention (intervention arm).
|
3.8%
1/26 • Number of events 1 • 2 years
Due to the severity of illness in this patient population, this study collected and reported Adverse Events only if at least possibly related to study participation, and only in patients undergoing study intervention (intervention arm).
|
Other adverse events
| Measure |
Group I: Observation
Group I (observation): Patients with full donor chimerism and no evidence of MRD continue to undergo clinical monitoring for acute and chronic graft-vs-host disease and relapse until 3 years post-transplant. Patients undergo repeat chimerism testing at 12 and 24 months post-transplant.
|
Group II: Intervention
n=26 participants at risk
Group II (intervention): Patients undergo withdrawal of immunosuppression and receive donor lymphocyte infusions between days 60-365 post-transplant (or until full donor chimerism is achieved). Patients also undergo clinical monitoring and repeat chimerism testing as in group I.
Withdrawal of immunosuppression and donor lymphocyte infusion: Intervention will involve fast withdrawal of immunosuppression and DLI until full donor chimerism is achieved.
|
|---|---|---|
|
Immune system disorders
aGVHD grade I-III
|
—
0/0 • 2 years
Due to the severity of illness in this patient population, this study collected and reported Adverse Events only if at least possibly related to study participation, and only in patients undergoing study intervention (intervention arm).
|
11.5%
3/26 • Number of events 3 • 2 years
Due to the severity of illness in this patient population, this study collected and reported Adverse Events only if at least possibly related to study participation, and only in patients undergoing study intervention (intervention arm).
|
|
Immune system disorders
cGVHD
|
—
0/0 • 2 years
Due to the severity of illness in this patient population, this study collected and reported Adverse Events only if at least possibly related to study participation, and only in patients undergoing study intervention (intervention arm).
|
7.7%
2/26 • Number of events 2 • 2 years
Due to the severity of illness in this patient population, this study collected and reported Adverse Events only if at least possibly related to study participation, and only in patients undergoing study intervention (intervention arm).
|
|
Blood and lymphatic system disorders
progressive disease
|
—
0/0 • 2 years
Due to the severity of illness in this patient population, this study collected and reported Adverse Events only if at least possibly related to study participation, and only in patients undergoing study intervention (intervention arm).
|
15.4%
4/26 • Number of events 4 • 2 years
Due to the severity of illness in this patient population, this study collected and reported Adverse Events only if at least possibly related to study participation, and only in patients undergoing study intervention (intervention arm).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place