Donor Lymphocyte Infusion After Alternative Donor Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 29, 2014