Expanded Access Protocol (EAP) Using the CliniMACS® Device for Pediatric Haplocompatible Donor Stem Cell Transplant

Expanded access is currently available for this treatment.
Verified May 2016 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01200017
First received: September 9, 2010
Last updated: May 18, 2016
Last verified: May 2016
  Purpose
This protocol provides expanded access to bone marrow transplants for children who lack a histocompatible (tissue matched) stem cell or bone marrow donor when an alternative donor (unrelated donor or half-matched related donor) is available to donate. In this procedure, some of the blood forming cells (the stem cells) are collected from the blood of a partially human leukocyte antigen (HLA) matched (haploidentical) donor and are transplanted into the patient (the recipient) after administration of a "conditioning regimen". A conditioning regimen consists of chemotherapy and sometimes radiation to the entire body (total body irradiation, or TBI), which is meant to destroy the cancer cells and suppress the recipient's immune system to allow the transplanted cells to take (grow). A major problem after a transplant from an alternative donor is increased risk of Graft-versus-Host Disease (GVHD), which occurs when donor T cells (white blood cells that are involved with the body's immune response) attack other tissues or organs like the skin, liver and intestines of the transplant recipient. In this study, stem cells that are obtained from a partially-matched donor will be highly purified using the investigational CliniMACS® stem cell selection device in an effort to achieve specific T cell target values. The primary aim of the study is to help improve overall survival with haploidentical stem cell transplant in a high risk patient population by limiting the complication of GVHD.

Condition Intervention
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Chronic Myeloid Leukemia
Myelodysplastic Syndrome
Lymphomas
Bone Marrow Failure
Hemoglobinopathy
Immune Deficiency
Osteopetrosis
Cytopenias
Leukocyte Disorders
Anemia Due to Intrinsic Red Cell Abnormality
Biological: CD34+ enriched, T Cell Depleted donor stem cell product

Study Type: Expanded Access     What is Expanded Access?
Official Title: An Expanded Access Study of the Feasibility of 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 University of California, San Francisco:

Study Start Date: September 2010
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: CD34+ enriched, T Cell Depleted donor stem cell product
    stem cell transplant
    Other Name: bone marrow transplant
Detailed Description:

Patients will be enrolled with alternative (mismatched/haplocompatible) related donors or unrelated donors either for an initial transplant or as a rescue following rejection of a previous graft or relapse following a previous transplant. For patients with mismatched related donors, the majority of clinical experience has been with a T cell-depleted PBSC product. Currently, no FDA-approved method for T cell depletion exists. Recent experience with the CliniMACS® device has produced excellent results with a 70-75% survival in children, many of whom were high risk patients.

Patients that receive transplants from unrelated donors usually receive stem cells that are not T cell-depleted. However, this is associated with a high risk of GVHD. The excellent results with mismatched related donor transplants justify expanding this approach to unrelated donor transplant recipients if the HLA mismatch is sufficiently great. It is anticipated that the use of the CliniMACS® device will result in a very low risk of GVHD without the need for post-transplant immunosuppression. The outcomes in relatively small studies for children receiving unrelated donor transplants using the CliniMACS® have been comparable to or better than those receiving T replete transplants with post-transplant immunosuppression.

This protocol will allow the use of patient-specific conditioning regimens. Some patients have contraindications to certain components of the conditioning regimen used for our ongoing study under BB-IND 8817 (CC# 01151). An example is a patient with pre-existing organ dysfunction that would be better served by the use of a reduced intensity conditioning regimen. Another example is a patient for whom total body irradiation is contraindicated due to very young age or prior radiation therapy. Finally, patients who would be otherwise eligible for the predecessor study but who do not have an eligible related donor or a closely matched unrelated donor would be eligible for this study. The target CD3+ T cell dose that will be given will be 3 x 104/kg. The UCSF 01151 protocol uses a dose of 3 x 104/kg. The T cell dose in the graft is usually < 1 x 104/kg after processing and T cells are added to the product.

  Eligibility

Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 0 (newborn) - 30 years
  • Patient must have a malignant or non-malignant disease that can benefit from alternative stem cell transplantation according to standard practice guidelines.
  • Patients with lymphoma or acute leukemia (except acute myeloid leukemia, AML) must be in remission at the time of transplant.
  • Patients must lack a healthy human leukocyte antigen (HLA)-identical related donor.
  • Recipient or authorized guardian must sign informed consent for this study.
  • If recipient is female and of child-bearing age, negative pregnancy test.
  • Patient must have a healthy, willing mismatched related or an unrelated donor who is:

    • Able to receive granulocyte colony-stimulating factor (G-CSF) and undergo apheresis either through placement of catheters in antecubital veins or a temporary central venous catheter,
    • For Related donor: sibling, half-sibling, parent, cousin, aunt, uncle or grandparent will all be considered eligible.
    • For Related donor: HLA antigen genotypic match ≥ 4/8 and ≤ 7/8 (haplocompatible).
    • For unrelated donor: 6/8 or 7/8 HLA antigen match (if two mismatches, they must be at different loci).
    • Complete medical history, physical and screening for infectious diseases that are acceptable for donation.
    • If donor is female and of child-bearing age, negative pregnancy test.
    • Absence of anti-HLA antibodies in recipient directed against donor antigens.
    • Donor must be willing to sign informed consent for this study. If donor is < 18 years of age, donor must be willing to give assent and parents willing to sign informed consent. For unrelated donors: The National Marrow Donor Program (NMDP) will obtain informed consent for donor's apheresis product to be used in this study.
    • Age ≥ 5 years

Exclusion Criteria:

  • Patient with an anticipated life expectancy of < 1 month
  • Active infectious hepatitis or cytomegalovirus (CMV) disease (organ involvement)
  • Human immunodeficiency virus (HIV) or Human T-lymphotropic virus (HTLV-I/II) infection
  • 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 (corrected for hemoglobin), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) <60% of predicted or oxygen saturation (O2 sat) > 94% on room air if unable to perform pulmonary function tests (PFTs); can be lower if a reduced intensity conditioning regimen is used.
  • Serum alanine aminotransferase (ALT) > 5 x upper limit of normal (can be up to 10x upper limit of normal if a reduced intensity conditioning regimen is used) or bilirubin > 2.
  • 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: NCT01200017

Contacts
Contact: Morton J. Cowan, MD 415-476-2188 mcowan@peds.ucsf.edu
Contact: Christopher Dvorak, MD 415-476-2188 DvorakC@peds.ucsf.edu

Locations
United States, California
University of California, San Francisco (UCSF) Children's Hospital
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Morton J. Cowan, MD UCSF Children's Hospital
  More Information

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01200017     History of Changes
Other Study ID Numbers: UCSF-10082 
Study First Received: September 9, 2010
Last Updated: May 18, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Genetic Diseases, Inborn
T cell depleted
Matched unrelated donors
Haplocompatible donors
Graft vs Host Disease
Hemoglobinopathies
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Myelodysplastic Syndromes
Preleukemia
Osteopetrosis
Pancytopenia
Immune System Diseases
Hematologic Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Myeloproliferative Disorders
Bone Marrow Diseases
Precancerous Conditions
Osteosclerosis
Osteochondrodysplasias
Bone Diseases, Developmental

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

ClinicalTrials.gov processed this record on July 25, 2016