Donor Lymphocyte Infusion After Alternative Donor Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to determine the ability of a donor lymphocyte infusion (DLI) given with methotrexate to hasten immune recovery without causing severe graft-versus-host disease (GVHD) in recipients who have had a T-cell depleted transplant.

Detailed Description
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Studies have shown that giving donor T cells after a mismatched T cell-depleted stem cell transplant can speed up recovery of T cells in the patient. This approach can cause severe graft versus host disease (GVHD). The purpose of this study is to determine whether giving a donor lymphocyte infusion (DLI) with methotrexate can accelerate immune recovery in recipients of T cell-depleted stem cell transplants. Thirty days after a T-cell depleted transplant, patients will be given a DLI. They will be monitored for immune recovery as measured by CD4 count and for GVHD toxicity. Patients will be separated into six cohorts based on dose of DLI received: 3 x 10^4, 4 x 10^4, 5 x 10^4, 6 X 10^4, 8 x 10^4, and 10 X10^4 cells/ kg of body weight. A minimum of 3 patients will be tested at each dose starting with the lowest dose. Dose escalation will continue until the dose associated with CD4 count >100 at Day +120 after transplant without significant GVHD is determined. All patients will receive thirteen doses of methotrexate after the DLI to prevent GVHD. Patients will be followed for 2 years for outcomes.

Official Title
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Phase I/II Study of Donor Lymphocyte Infusion With Methotrexate GVHD Prophylaxis to Hasten Immune Reconstitution After CD34+ Cell-Selected Transplant

Conditions
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Immunodeficiency

Intervention / Treatment
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* Biological: Infusion of donor lymphocytes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have been treated on the LCH BMT 09-01 protocol Signed informed consent by patient or legal guardian Exclusion Criteria: Active GVHD at the time when DLI are due History of acute GVHD > grade I prior to DLI Disease due to viral infection (eg. CMV) when DLI are due (asymptomatic viral replication or viral shedding is not a contraindication) Uncontrolled bacterial or fungal infection O2 saturation by pulse oximetry < 95% Bilirubin > 3mg/dL or ALT > 5 x upper limit of normal Creatinine > 3x baseline (at transplant) ANC (WBC x % neutrophils + bands) < 500/ul Significant effusions (eg. pleural or pericardial) or ascites EBV-related PTLD Persistent or increasing mixed chimerism requiring therapeutic DLI as defined on the LCH BMT 09-01 protocol

Ages Eligible for Study
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Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infusion of donor lymphocytes<br>Patients will receive an infusion of donor lymphocyte after T-cell depleted transplant. | Biological: Infusion of donor lymphocytes<br>* A donor lymphocyte infusion will be given to provide T cells. There will be a dose escalation: 3 x 10^4, 4 x 10^4, 5 x 10^4, 6 X 10^4, 8 x 10^4, and 10 X10^4 cells/kg body weight. At least three patients will be assessed at each dose to determine safety before dose is increased.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Immune Recovery Following Transplantation | Immune recovery was measured by CD4+ cells > 100/μL by Day 120 following transplantation | 120 days after transplant | 
| Incidence and Severity of GVHD | Patients were evaluated for acute GVHD due to prophylactic DLI between the day of prophylactic DLI infusion and Day +180 after transplant. GVHD was graded using standard criteria. | 180 days after transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Infection and EBV-related Post-transplant Lymphoproliferative Disease (PTLD) | Subjects were actively monitored for adenovirus, cytomegalovirus (CMV), human herpes virus 6 (HHV6), and Epstein-Barr virus (EBV) as part of standard post-transplant care. All infections were collected from date of DLI until 1 year after transplant. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Donor Lymphocyte Infusion, Immune Recovery, T cell depleted transplant, Mismatched related donor transplants, Unrelated donor transplants