Standardization of CD3+ T Cell Dose for Patients Receiving Allogeneic Peripheral Blood Stem Cell Transplantation From Matched Related Donors
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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 |
- 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 ]
- 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) |
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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.
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 |
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:
- AML/ALL: with Bi-phenotypic features
- AML: Refractory to Induction and salvage therapy
- ALL: Refractory to Induction and salvage therapy
- ALL: t(9;22) Philadelphia Chromosome positive disease
- CML: Active blast crisis
- HL: Disease refractory to chemotherapy or targeted therapy
- NHL: Disease refractory to chemotherapy or targeted therapy
- HIV positive
Contacts and Locations| Contact: William P Vaughan, MD | 205-934-9695 | wvaughan@uab.edu |
| Contact: Lisa D Williams, RN | 205-934-0066 | LiWilliams@uabmc.edu |
| United States, Alabama | |
| University of Alabama Hospital | Recruiting |
| Birmingham, Alabama, United States, 35294 | |
| Contact: William P Vaughan, MD 205-934-9695 wvaughan@uab.edu | |
| Principal Investigator: William P Vaughan, MD | |
| Sub-Investigator: Donna E. Salzman, MD | |
| Sub-Investigator: Richard D. Lopez, MD | |
| Sub-Investigator: Racquel Innis-Shelton, MD | |
| Principal Investigator: | William P Vaughan, MD | University of Alabama in Birmingham |
More Information
Additional 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: | January 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 May 23, 2013