Donor Lymphocyte Infusion After Alternative Donor Transplantation

This study is currently recruiting participants.
Verified March 2014 by Carolinas Healthcare System
Sponsor:
Information provided by (Responsible Party):
Andrew Gilman, Carolinas Healthcare System
ClinicalTrials.gov Identifier:
NCT01027702
First received: December 7, 2009
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Immunocompromised After T-cell Depleted Transplant.
Biological: Infusion of donor lymphocytes
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Donor Lymphocyte Infusion With Methotrexate GVHD Prophylaxis to Hasten Immune Reconstitution After CD34+ Cell-Selected Transplant

Further study details as provided by Carolinas Healthcare System:

Primary Outcome Measures:
  • Immune recovery following transplantation [ Time Frame: 120 days after transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence and severity of GVHD [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Determine incidence of infection and EBV-related post-transplant lymphoproliferative disease (PTLD) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: August 2009
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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 +100 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

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01027702

Contacts
Contact: Andrew Gilman, MD 704-381-9902 andrew.gilman@carolinashealthcare.org
Contact: Tracy Fukes, RN 980-442-2310 tracy.fukes@carolinashealthcare.org

Locations
United States, North Carolina
Levine Children's Hospital, Carolinas Medical Center Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Andrew Gilman, MD    704-381-9902    andrew.gilman@carolinashealthcare.org   
Contact: Tracy Fukes, RN    980-442-2310    tracy.fukes@carolinashealthcare.org   
Principal Investigator: Andrew Gilman, MD         
Sub-Investigator: Michael Eckrich, MD         
Sub-Investigator: Javier Oesterheld, MD         
Sub-Investigator: Alexis F Teplick, MD         
Sponsors and Collaborators
Andrew Gilman
Investigators
Principal Investigator: Andrew Gilman, MD Department of Pediatrics, Levine Children's Hospital, Carolinas Healthcare System
  More Information

No publications provided

Responsible Party: Andrew Gilman, Director, Pediatric Blood and Marrow Transplantation, Carolinas Healthcare System
ClinicalTrials.gov Identifier: NCT01027702     History of Changes
Other Study ID Numbers: LCH BMT 09-02
Study First Received: December 7, 2009
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Carolinas Healthcare System:
Donor Lymphocyte Infusion
Immune Recovery
T cell depleted transplant
Mismatched related donor transplants
Unrelated donor transplants

ClinicalTrials.gov processed this record on April 15, 2014