We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Donor Lymphocyte Infusion After Alternative Donor Transplantation

This study has been terminated.
(Sponsor/ PI leaving institution, no plans to continue this research at this time)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01027702
First Posted: December 9, 2009
Last Update Posted: November 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Andrew Gilman, Carolinas Healthcare System
  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
Immunodeficiency Biological: Infusion of donor lymphocytes Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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 Andrew Gilman, Carolinas Healthcare System:

Primary Outcome Measures:
  • Number of Participants With Immune Recovery Following Transplantation [ Time Frame: 120 days after transplant ]
    Immune recovery was measured by CD4+ cells > 100/μL by Day 120 following transplantation

  • Incidence and Severity of GVHD [ Time Frame: 180 days after transplant ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Infection and EBV-related Post-transplant Lymphoproliferative Disease (PTLD) [ Time Frame: 1 year ]
    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.


Enrollment: 38
Study Start Date: August 2009
Study Completion Date: November 2016
Primary Completion Date: November 2016 (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 +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

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01027702


Locations
United States, North Carolina
Levine Children's Hospital, Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
Sponsors and Collaborators
Andrew Gilman
Investigators
Principal Investigator: Andrew Gilman, MD Department of Pediatrics, Levine Children's Hospital, Carolinas Healthcare System
  Study Documents (Full-Text)

Documents provided by Andrew Gilman, Carolinas Healthcare System:
Informed Consent Form  [PDF] July 31, 2017

  More Information

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
First Submitted: December 7, 2009
First Posted: December 9, 2009
Results First Submitted: September 9, 2017
Results First Posted: November 8, 2017
Last Update Posted: November 8, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Immune System Diseases