Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Standardization of CD3+ T Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Related Donors

This study has suspended participant recruitment.
(Protocol being amended to include new data on optimum CD3 dose.)
Sponsor:
Collaborator:
Miltenyi Biotec, Inc.
Information provided by (Responsible Party):
William P. Vaughan, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00959140
First received: August 12, 2009
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

Stem cells collected from sibling donors for allogenic transplants contain various types of cells. The predominant immune cells are called CD3+ T cells. The amount of these T cells vary vastly from donor to donor. This study is to determine if standardizing the CD3+ T cell dose will benefit the recipient (patient). As well as to help discover if dose standardization causes less variation in outcomes between patients and to make transplantation more predictable and complications easier to manage.


Condition Intervention Phase
Hematopoietic Stem Cell Transplantation
Device: CD3+ T cell depletion
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Phase II Study for Standardization of CD3+ T Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplants From Matched Related Donors

Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Incidence and severity of acute graft versus host disease (aGVHD) with the chosen fixed dose of CD3+ cells [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to engraftment [ Time Frame: 60 days ] [ Designated as safety issue: Yes ]
  • State of chimerism over time [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Immune reconstitution over time [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Incidence, severity and organ involvement with chronic GVHD (cGVHD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Disease free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: October 2008
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Device: CD3+ T cell depletion

    The peripheral blood stem cell product is engineered to deliver a dose of 3.0+/-0.5 x107 CD3+ cells/kg recipient body weight. Other components of the graft will not be manipulated and the recipient will receive the total number of cells collected with the exception of minimal losses that occur during the process of CD3+ T cell isolation. Following collection, CD3+ T cells will be enumerated and a portion of the product containing 3.0 x107 CD 3+ cells/kg will be set aside. The remainder of the product will be depleted of CD3+ T cells.

    Following CD3+ T cell depletion, the CD3+ T cell depleted product will then be combined with the unmanipulated product to provide the specified levels of CD3+ T cells/kg recipient body-weight. The graft is infused into the patient on the same day as selected and within 24 hours of donor aphaeresis.

Detailed Description:

The optimal CD3+ cell dose to be used for allo HSCT is unknown. In addition, there are multiple variables in addition to CD3+ cell dose which affect engraftment, immune reconstitution, GVH and GVL in these patients including recipient age, diagnosis, disease status at transplantation, donor/recipient tissue type match, preparative regimen, and GVHD prophylaxis. Thus the ability to produce products with a fixed CD3+ content is critical to further research and ultimately to the definition of the "right dose" of CD3+ cells for various clinical situations.

Patients who meet eligibility criteria will receive a peripheral blood stem cell product from their original matched sibling donor engineered to deliver a dose of 3.0+/-0.5 x107 CD3+ cells/kg recipient body weight. Other components of the graft will not be manipulated and the recipient will receive the total number of cells collected with the exception of minimal losses that occur during the process of CD3+ T cell isolation.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be 19 years of age or greater .
  • Patients must meet all the UAB diagnosis and disease status criteria for clinical appropriateness for allo HSCT derived from ASBMT and NCCN guidelines and updated annually.
  • Patients must have a 10/10 matched sibling peripheral blood progenitor cell donor
  • Patients must receive a myeloablative preparative regimen containing busulfan targeted to an AUC of 1000/ dose for 16 doses combined with fludarabine 40 mg/M2 daily for 4 days.
  • Patients must not have any significant organ system compromise except hematopoiesis as defined in the UAB eligibility checklist including, a Karnofsky performance status>70% and a life expectancy assuming control of primary disease > 8 weeks.
  • Patients must be capable of understanding of the nature of their disease and willingly give consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
  • Patients must have signed informed consent both for this study and the research use of data in the UAB BMT Program's IRB registered clinical database.
  • All patients, irrespective of participation in a clinical trial, must have a signed informed consent for the performance of matched related donor transplantation.

Exclusion Criteria:

  • Serious active infection not controlled by antibiotics.
  • Prior autologous or allogeneic transplantation for any disease.
  • High Risk Features associated with increased relapse risk or poor outcomes:

    1. AML/ALL: with Bi-phenotypic features
    2. AML: Refractory to Induction and salvage therapy
    3. ALL: Refractory to Induction and salvage therapy
    4. ALL: t(9;22) Philadelphia Chromosome positive disease
    5. CML: Active blast crisis
    6. HL: Disease refractory to chemotherapy or targeted therapy
    7. NHL: Disease refractory to chemotherapy or targeted therapy
    8. HIV positive
  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: NCT00959140

Locations
United States, Alabama
University of Alabama Hospital
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
William P. Vaughan, MD
Miltenyi Biotec, Inc.
Investigators
Principal Investigator: William P Vaughan, MD University of Alabama in Birmingham
  More Information

No publications provided

Responsible Party: William P. Vaughan, MD, Professor, Internal Medicine and Pharmacology, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00959140     History of Changes
Other Study ID Numbers: UAB 0624
Study First Received: August 12, 2009
Last Updated: June 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Alabama at Birmingham:
Allo PBSC
HSCT
Bone Marrow Transplant
Allogeneic Bone Marrow Transplant
Matched Related Donor Transplant
MRD HSCT

ClinicalTrials.gov processed this record on November 20, 2014