T-cell Depleted Alternative Donor Transplantation

NCT00968864 | Terminated Phase 2 Results DMC

• 1 other identifier: LCH BMT 09-01
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Myelodysplastic Syndrome; Lymphomas; Bone Marrow Failure; Hemoglobinopathy; Immune Deficiency; Osteopetrosis

Keywords

T cell depleted; Matched unrelated donors; Haplocompatible donors

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Severe Graft vs. Host Disease (GVHD).

  Severe GVHD defined as grade III/IV GVHD.

  Within 30 days after stem cell transplant

Secondary Outcomes (8)

• Number of Participants With Engraftment and Time to Engraftment

  Within 28 days after stem cell transplant

• Number of Participants With Post-transplant Infections

  1 year

• Number of Participants With EBV-related Post Transplant Lymphoproliferative Disorder (PTLD)

  5 years

• Number of Participants With Post-transplant Leukemia Relapse

  5 years

• Number of Participants With Transplant-related Mortality

  2 year

Study Arms (1)

CliniMACS® (T cell depletion)

EXPERIMENTAL

Recipients will receive T cell-depleted PBSC from eligible donors after receiving conditioning therapy using CliniMACS® device.

Device: CliniMACS® (T cell depletion)

Interventions

CliniMACS® (T cell depletion) 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.

Also known as: CliniMACS device, T-cell depletion

CliniMACS® (T cell depletion)

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• Able to receive G-CSF and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter,
• Healthy,
• Willing,
• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Levine Children's Hospital, Carolinas Medical Center

Charlotte, North Carolina, 28204, United States

Location

Related Publications (1)

• 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.

  PMID: 29296761 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Lymphoma; Bone Marrow Failure Disorders; Hemoglobinopathies; Immunologic Deficiency Syndromes; Osteopetrosis

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases

Results Point of Contact

• Title: Dr. Andrew Gilman
• Organization: PRA Health Sciences

gilmanandy@prahs.com

704-615-2744

Study Officials

• Andrew Gilman, MD

  Department of Pediatrics, Levine Children's Hospital, Carolinas Healthcare System

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2009
• First Posted: August 31, 2009
• Study Start: August 1, 2009
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: April 22, 2022
• Results First Posted: November 8, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)