Overview

This trial is active, not recruiting.

Conditions acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloid leukemia, myelodysplastic syndrome, lymphomas, bone marrow failure, hemoglobinopathy, immune deficiency, osteopetrosis
Treatment clinimacs® (t cell depletion)
Phase phase 2
Sponsor Andrew Gilman
Start date August 2009
End date June 2019
Trial size 53 participants
Trial identifier NCT00968864, LCH BMT 09-01

Summary

The primary purpose is to determine the ability of CD34+ selection and T cell depletion using the CliniMACS® device to prevent severe acute graft-versus-host disease (GVHD) in patients receiving a stem cell transplant from an alternative (unrelated and mismatched related) donor. The secondary objectives include evaluation of engraftment, immune recovery, and post-transplant infections.

Patients requiring stem cell transplants for either malignant (cancerous) or non-malignant disease will be included in the study. The recipients will be grouped into one of two groups based on whether the donor is mismatched related (Cohort A) or unrelated (Cohort B). The patient will receive a conditioning regimen including chemotherapy drugs and/or total body irradiation based on the disease for which the transplant is performed.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device.
clinimacs® (t cell depletion) CliniMACS device
Stem cells will be collected from donors after they receive Granulocyte colony-stimulating factor (G-CSF). The cells will be processed using the CliniMACS device to select for CD34+ stem cells and to deplete T cells. Recipients will receive conditioning therapy that is based on their disease type and then receive the CD34+ stem cells.

Primary Outcomes

Measure
Determine rate of severe GVHD.
time frame: Within 30 days after stem cell transplant

Secondary Outcomes

Measure
Evaluate the rate of engraftment
time frame: Within 28 days after stem cell transplant
Evaluate post-transplant infections
time frame: 5 years
Evaluate rate of EBV-related post transplant lymphoproliferative disorder (PTLD)
time frame: 5 years
Evaluate post-transplant leukemia relapse
time frame: 5 years
Evaluate transplant-related mortality
time frame: 5 years
Evaluate transplant-related toxicities
time frame: 5 years
Evaluate overall survival
time frame: 5 years
Monitor device performance: purity of selected product, yield of CD34+ cells, CD3+ cell depletion, viability and sterility.
time frame: Length of the trial (5 years)

Eligibility Criteria

Male or female participants up to 30 years old.

Inclusion Criteria: - Age < 30 years - Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation. Examples include acute and chronic leukemias, myelodysplastic syndrome, lymphoma, severe acquired and congenital cytopenias, white and red blood cell abnormalities, and immunodeficiencies. - Patients with acute lymphoblastic leukemia must be in morphological remission (< 5% blasts) at the time of transplant. Patients with acute non-lymphocytic leukemia will preferably be in morphologic remission but may be enrolled when aplastic after chemotherapy or with < 20% blasts. Patients with lymphoma must be in complete or close to complete remission (if residual adenopathy, PET scan must be negative or only have slight uptake, eg. SUV < 2). - Patients must lack a healthy HLA-identical related donor of at least one year of age. - Patient must have a mismatched related or an unrelated donor who is: 1. Able to receive G-CSF and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter, 2. Healthy, 3. Willing, 4. For recipients of an unrelated donor transplant, recipient eligibility will be restricted as follows if in the judgment of the recipients' transplant physician, the recipient cannot receive a transplant with combined positive and negative fractions as described in Section 6.1.3.2 or an unmanipulated PBSC product. 5. Meets eligibility criteria for donors. - If only one mismatched related relative is available, an acceptable unrelated donor must be identified as a backup. - Patient or authorized guardian must sign informed consent for this study. Exclusion Criteria: - Patient with an anticipated life expectancy of < 1 month - Active infectious hepatitis or CMV infection - HIV or HTLV-I/II infection - Serious infection (bacterial, fungal, viral) within the last 4 weeks - Cardiac ejection fraction < 45%; can be lower if patient is not in clinical cardiac failure and a reduced intensity conditioning regimen is used. - Creatinine clearance <60 ml/min/1.72 m2; can be lower if a reduced intensity conditioning regimen is used. - Pulmonary diffusion capacity (adjusted for Hgb), FEV1, or FVC <60% of predicted or O2 sat < 94% if unable to perform PFTs; can be lower if a reduced intensity conditioning regimen is used. - Serum ALT > 3 x upper limit of normal (can be up to 5 x upper limit of normal if a reduced intensity conditioning regimen is used) or bilirubin > 2. The bilirubin criteria for sickle cell disease patients is direct bilirubin >2x upper limit of normal. - Performance score (Lansky/Karnofsky) < 50 - Any condition that compromises compliance with the procedures of this protocol, as judged by the principal investigator.

Additional Information

Official title A Phase II Study Using the CliniMACS® Device for CD34+ Cell Selection and T Cell Depletion for Graft-versus-Host Disease Prophylaxis in Alternative Donor Stem Cell Transplant Recipients
Principal investigator Andrew Gilman, MD
Description A major issue in alternative donor (mismatched related and unrelated donor transplantation is the development of graft-versus-host disease (GVHD). Several clinical trials have shown that the use of T-cell depleted peripheral blood stem cells (PBSC) reduces GVHD in alternative donor transplants. The purpose of this study is to determine the ability of CD34 positive selection and T cell depletion using the CliniMACS® Device as the only GVHD prophylaxis to prevent severe acute GVHD in recipients of an alternative donor PBSC transplant. Mismatched related donors will match at least 3 of 6 Human leukocyte antigens(HLA)(haplocompatible) and unrelated donors will match at least 6 out of 8 HLA antigens with the transplant recipient. The conditioning therapy including chemotherapy, anti-thymocyte globulin (ATG), +/- total body irradiation (TBI) will be based on the patient's diagnosis. The transplant recipient will be followed for 5 years after transplant for GVHD, engraftment, post-transplant infections, disease relapse, and overall survival. In addition, this study will serve as a platform for a companion study of therapy to accelerate immune recovery after transplant.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Carolinas Healthcare System.