Donor Lymphocyte Infusion After Alternative Donor Transplantation

Immunodeficiency Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01027702
• Other study ID #: LCH BMT 09-02
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: August 2009
• Est. completion date: November 2016

Study information

• Verified date: October 2017
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• Immunodeficiency
• Immunologic Deficiency Syndromes

Intervention

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.

Locations

Country	Name	City	State
United States	Levine Children's Hospital, Carolinas Medical Center	Charlotte	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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