T-cell Depleted Alternative Donor Transplantation

• ClinicalTrials.gov Identifier: NCT00968864
• Recruitment Status: Terminated
• First Posted: August 31, 2009
• Results First Posted: November 8, 2017
• Last Update Posted: November 8, 2017
• Sponsor: Andrew Gilman
• Information provided by (Responsible Party): Andrew Gilman, Atrium Health

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Myelodysplastic Syndrome; Lymphomas; Bone Marrow Failure; Hemoglobinopathy; Immune Deficiency; Osteopetrosis	Device: CliniMACS® (T cell depletion)	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: August 2009
• Actual Primary Completion Date: November 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm

Intervention/treatment

Experimental: CliniMACS® (T cell depletion); 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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Severe Graft vs. Host Disease (GVHD). [ Time Frame: Within 30 days after stem cell transplant ]
   Severe GVHD defined as grade III/IV GVHD.

Secondary Outcome Measures :

1. Number of Participants With Engraftment and Time to Engraftment [ Time Frame: Within 28 days after stem cell transplant ]
   Engraftment was measured as time to absolute neutrophil count >500
2. Number of Participants With Post-transplant Infections [ Time Frame: 1 year ]
3. Number of Participants With EBV-related Post Transplant Lymphoproliferative Disorder (PTLD) [ Time Frame: 5 years ]
4. Number of Participants With Post-transplant Leukemia Relapse [ Time Frame: 5 years ]
5. Number of Participants With Transplant-related Mortality [ Time Frame: 2 year ]
   Transplant-related mortality includes death due to regimen-related toxicity or GVHD (all causes other than disease relapse). Those who died due to disease relapse are not included in the analyzed population for that time point.
6. Number of Participants With Transplant-related Toxicities [ Time Frame: 1 year ]
7. Overall Survival [ Time Frame: 2 years ]
8. Device Performance: Dose of CD34+ Cells and CD3+ Cells Given [ Time Frame: Length of the trial (5 years) ]

   For mismatched related donors, the target cell dose after processing is >/= 20 x 10^6 CD34+ cells/kg patient body weight, but >/= 8 x 10^6 is acceptable.

   For unrelated donors the target cell dose after processing is >/= 10 x 10^6 CD34+ cells/kg patient body weight, but >/= 4 x 10^6 is acceptable.

   The target T cell dose is </= 3 x 10^4 CD3+ cells/ kg.

Eligibility Criteria

• Ages Eligible for Study: up to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, North Carolina

Levine Children's Hospital, Carolinas Medical Center

Charlotte, North Carolina, United States, 28204

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, Atrium Health:

Study Protocol and Statistical Analysis Plan  [PDF] January 30, 2015

Informed Consent Form: Recipient Consent  [PDF] January 30, 2015

Informed Consent Form: Donor Consent  [PDF] March 11, 2014

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Gilman AL, Eckrich MJ, Epstein S, Barnhart C, Cannon M, Fukes T, Hyland M, Shah K, Grochowski D, Champion E, Ivanova A. Alternative donor hematopoietic stem cell transplantation for sickle cell disease. Blood Adv. 2017 Jun 28;1(16):1215-1223. doi: 10.1182/bloodadvances.2017005462. eCollection 2017 Jul 11.

• Responsible Party: Andrew Gilman, Director, Pediatric Blood and Marrow Transplantation, Atrium Health
• ClinicalTrials.gov Identifier: NCT00968864
• Other Study ID Numbers: LCH BMT 09-01
• First Posted: August 31, 2009
• 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, Atrium Health:

T cell depleted; Matched unrelated donors; Haplocompatible donors

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Osteopetrosis; Myelodysplastic Syndromes; Hemoglobinopathies; Bone Marrow Failure Disorders; Pancytopenia; Immunologic Deficiency Syndromes; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Genetic Diseases, Inborn; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases