T-cell Depleted Alternative Donor Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Carolinas Healthcare System
Information provided by (Responsible Party):
Andrew Gilman, Carolinas Healthcare System
ClinicalTrials.gov Identifier:
First received: August 28, 2009
Last updated: February 5, 2016
Last verified: February 2016

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.

Condition Intervention Phase
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Chronic Myeloid Leukemia
Myelodysplastic Syndrome
Bone Marrow Failure
Immune Deficiency
Device: CliniMACS® (T cell depletion)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Carolinas Healthcare System:

Primary Outcome Measures:
  • Determine rate of severe GVHD. [ Time Frame: Within 30 days after stem cell transplant ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the rate of engraftment [ Time Frame: Within 28 days after stem cell transplant ] [ Designated as safety issue: Yes ]
  • Evaluate post-transplant infections [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Evaluate rate of EBV-related post transplant lymphoproliferative disorder (PTLD) [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Evaluate post-transplant leukemia relapse [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Evaluate transplant-related mortality [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Evaluate transplant-related toxicities [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • Evaluate overall survival [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 90
Study Start Date: August 2009
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T cell depletion using CliniMACS®
Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device.
Device: CliniMACS® (T cell depletion)
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.
Other Names:
  • CliniMACS device
  • T-cell depletion

Detailed 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.

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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 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.
  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: NCT00968864

Contact: Andew Gilman, MD 704-381-9902 andrew.gilman@carolinashealthcare.org
Contact: Mark W Cannon 980-442-2324 mark.cannon@carolinashealthcare.org

United States, North Carolina
Levine Children's Hospital, Carolinas Medical Center Recruiting
Charlotte, North Carolina, United States, 28204
Contact: Andrew Gilman, MD    704-381-9902    andrew.gilman@carolinashealthcare.org   
Contact: Mark W Cannon    980-442-2324    mark.cannon@carolinashealthcare.org   
Principal Investigator: Andrew Gilman, MD         
Sub-Investigator: Michael Eckrich, MD         
Sub-Investigator: Javier Oesterheld, MD         
Sponsors and Collaborators
Andrew Gilman
Principal Investigator: Andrew Gilman, MD Department of Pediatrics, Levine Children's Hospital, Carolinas Healthcare System
  More Information

Responsible Party: Andrew Gilman, Director, Pediatric Blood and Marrow Transplantation, Carolinas Healthcare System
ClinicalTrials.gov Identifier: NCT00968864     History of Changes
Other Study ID Numbers: LCH BMT 09-01 
Study First Received: August 28, 2009
Last Updated: February 5, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Carolinas Healthcare System:
T cell depleted
Matched unrelated donors
Haplocompatible donors

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Leukemia, Lymphoid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Bone Diseases
Bone Diseases, Developmental
Bone Marrow Diseases
Genetic Diseases, Inborn
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Musculoskeletal Diseases
Myeloproliferative Disorders
Neoplasms by Histologic Type
Precancerous Conditions

ClinicalTrials.gov processed this record on May 04, 2016