Donor Lymphocyte Infusion After Alternative Donor Transplantation

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

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.

Study Overview

• Status: Terminated
• Conditions: Immunodeficiency
• Intervention / Treatment: Biological: Infusion of donor lymphocytes

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Levine Children's Hospital, Carolinas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 30 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Infusion of donor lymphocytes; Patients will receive an infusion of donor lymphocyte after T-cell depleted transplant.	Biological: Infusion of donor lymphocytes; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (ACTUAL): November 1, 2016
• Study Completion (ACTUAL): November 1, 2016

Study Registration Dates

• First Submitted: December 7, 2009
• First Submitted That Met QC Criteria: December 8, 2009
• First Posted (ESTIMATE): December 9, 2009

Study Record Updates

• Last Update Posted (ACTUAL): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Donor Lymphocyte Infusion; Immune Recovery; T cell depleted transplant; Mismatched related donor transplants; Unrelated donor transplants
• Additional Relevant MeSH Terms: Immune System Diseases; Immunologic Deficiency Syndromes
• Other Study ID Numbers: LCH BMT 09-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO