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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by University of Alabama at Birmingham
Sponsor:
Collaborator:
Miltenyi Biotec, Inc.
Information provided by (Responsible Party):
Ayman Saad, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00959140
First received: August 12, 2009
Last updated: April 20, 2015
Last verified: April 2015
  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 2014
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CD3+ T-cell depletion
CD3+ T-cell depletion
Device: CD3+ T cell depletion

The peripheral blood stem cell product is engineered to deliver a dose of 15 to 20 x10^7 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 15 to 20 x10^7 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:

  1. Patients must be ≥19 years of age.
  2. Patients must meet all the UAB diagnosis and disease status criteria for clinical appropriateness for myeloablative allo HSCT derived from ASBMT and NCCN guidelines.
  3. Patients must have a 10/10 HLA matched sibling (excluding identical twin). All donors will be evaluated for eligibility and suitability per standard of care according FACT and NMDP guidelines.
  4. Adequate organ function: All organ function testing should be done within 28 days of study registration.
  5. Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
  6. Pulmonary: FEV1 (Forced expiratory volume in 1 second) and FVC (Forced vital capacity) ≥ 50% predicted, DLCO (alveolar diffusion capacity for carbon monoxide) (corrected for hemoglobin) ≥ 50% of predicted.
  7. Renal: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula
  8. Performance status: Karnofsky ≥ 70%
  9. Hepatic (values to be less than what is considered grade II toxicity per the CTCAE (common terminology criteria for adverse events)

Exclusion criteria

  1. Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection by imaging studies such as chest CT scan within 14 days of registration.
  2. HIV positive patients.
  3. Prior autologous or allogeneic transplantation for any disease.
  4. Scheduled to receive non-myeloablative or reduced intensity conditioning regimen.
  5. 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. CML: Active blast crisis
    5. HL: Disease refractory to chemotherapy or targeted therapy
    6. NHL: Disease refractory to chemotherapy or targeted therapy
  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

Contacts
Contact: Ayman Saad, MD 205-934-1908 aasaad@uab.edu
Contact: Lisa D Williams, RN 205-934-0066 LiWilliams@uabmc.edu

Locations
United States, Alabama
University of Alabama Hospital Recruiting
Birmingham, Alabama, United States, 35294
Contact: Ayman A Saad, MD    205-934-1908    aasaad@uab.edu   
Contact: Lisa D Williams, RN    205-934-0066    liwilliams@uabmc.edu   
Sub-Investigator: Donna E. Salzman, MD         
Sub-Investigator: Racquel Innis-Shelton, MD         
Sub-Investigator: Antonio Di Stasi, MD         
Sub-Investigator: Shin Mineishi, MD         
Principal Investigator: Ayman Saad, MD         
Sub-Investigator: Luciano Costa, MD         
Sponsors and Collaborators
Ayman Saad
Miltenyi Biotec, Inc.
Investigators
Principal Investigator: Ayman Saad, MD University of Alabama in Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: Ayman Saad, Associate Professor of Medicine, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00959140     History of Changes
Other Study ID Numbers: UAB 1410
Study First Received: August 12, 2009
Last Updated: April 20, 2015
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 August 27, 2015