Clinical trial NCT01027702: Donor Lymphocyte Infusion After Alternative Donor Transplantation
Official title: Phase I/II Study of Donor Lymphocyte Infusion With Methotrexate GVHD Prophylaxis to Hasten Immune Reconstitution After CD34+ Cell-Selected Transplant
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Immunodeficiency
Keywords: Donor Lymphocyte Infusion
Immune Recovery
T cell depleted transplant
Mismatched related donor transplants
Unrelated donor transplants
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2009-12-09
Enrollment: 38
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Immune Recovery Following Transplantation
timeFrame: 120 days after transplant
measure: Incidence and Severity of GVHD
timeFrame: 180 days after transplant
Secondary outcomes:
measure: Number of Participants With Infection and EBV-related Post-transplant Lymphoproliferative Disease (PTLD)
timeFrame: 1 year
Other outcomes:
Locations:
city: Charlotte
country: United States
facility: Levine Children's Hospital, Carolinas Medical Center
state: North Carolina
Study officials:
affiliation: Department of Pediatrics, Levine Children's Hospital, Carolinas Healthcare System
name: Andrew Gilman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gilman AL, Leung W, Cowan MJ, Cannon M, Epstein S, Barnhart C, Shah K, Hyland M, Fukes T, Ivanova A. Donor lymphocyte infusion and methotrexate for immune recovery after T-cell depleted haploidentical transplantation. Am J Hematol. 2018 Feb;93(2):169-178. doi: 10.1002/ajh.24949. Epub 2017 Nov 17.