A Two-Step Approach to Bone Marrow Transplant Using Cells From A Partially-Matched Relative
The purpose of this study is to develop a way of treating patients who do not have a completely matched family donor or a readily available unrelated donor with bone marrow transplant by using a partially-matched family donor. Patients receiving this type of transplant will receive chemotherapy and/or radiation to treat their disease. They will also receive their donor's cells in 2 parts. During the first part, the donor's lymphocytes will be exposed to one of the chemotherapy agents to help the patient become tolerant to the lymphocytes. In the second part of the transplant, the patient will receive their donor's stem cells to help recover their peripheral blood counts and establish long-term engraftment. The hypothesis of this study is that in partially-matched allogeneic transplant, there is a defined number of donor T-cells that can be treated and given to the recipient to avoid post-transplant infection without causing severe graft-versus-host disease.
Radiation: Total Body Irradiation (TBI)
Biological: Donor Lymphocyte Infusion (DLI)
Drug: Cyclophosphamide (CY)
Drug: Mycophenolate Mofetil (MMF)
Biological: Hematopoietic Stem Cell Transplant (HSCT)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Two Step Approach To Allogeneic Hematopoietic Stem Cell Transplantation for Hematologic Malignancies From HLA Partially-Matched Related Donors|
- Overall Survival of Participants [ Time Frame: 6 months ] [ Designated as safety issue: No ]To determine overall survival at 6 months post-transplant.
- Optimal Dose of CD3+ Donor Lymphocytes (T-cells) for Consistent Engraftment Without GVHD [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
To determine the optimal dose of CD3+ donor lymphocytes required for consistent engraftment without the development of grade III/IV GVHD.
Measured as CD3+ donor lymphocytes given as n x 10^8/kg.
"n" was found to be 2 and was found to be the optimal dose and was the only dose given.
- Engraftment Rates [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]To assess hematopoietic engraftment rates.
- Lymphoid Recovery [ Time Frame: 6 months ] [ Designated as safety issue: No ]To assess the pace of lymphoid recovery in this patient population.
- Incidence of Grades III-IV GVHD [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
To determine the incidence and severity of GVHD in these patients using a combination of cyclophosphamide, tacrolimus and mycophenolate mofetil (MMF) as GVHD prophylaxis.'
Severity was graded using CTCAE 3.0 (1=mild, 2=moderate, 3=severe, 4=life threatening/disabling, 5=death)
|Study Start Date:||January 2006|
|Study Completion Date:||June 2010|
|Primary Completion Date:||August 2009 (Final data collection date for primary outcome measure)|
Experimental: Haploidentical Allogeneic Transplantation
Patients undergoing hematopoietic stem cell transplant from a partially matched related donor
Radiation: Total Body Irradiation (TBI)
TBI twice daily days 6-9 prior to transplant (HSCT)
Other Names:Biological: Donor Lymphocyte Infusion (DLI)
DLI given 6 days prior to transplant (HSCT).
Other Names:Drug: Cyclophosphamide (CY)
Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT).
Other Names:Drug: Tacrolimus
Tacrolimus given one day prior to transplant (HSCT).
Other Names:Drug: Mycophenolate Mofetil (MMF)
MMF given one day prior to transplant (HSCT).
Other Names:Biological: Hematopoietic Stem Cell Transplant (HSCT)
CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed. This is the day of transplantation.
Haploidentical hematopoietic stem cell transplant is a life-saving therapy for patients who are without well matched donors. This type of therapy has been associated with poor outcomes in the past due to complications such as infection. The Jefferson 2 Step approach was designed to allow the infusion of an exact dose of tolerized lymphocytes in haploidentical transplant in order to allow for immune reconstitution post transplant to avoid infectious complications while still having acceptable rates of GVHD. In this approach, patients with high-risk hematological malignancies undergo 8 fractions of TBI (12 Gy) followed by an exact dose of donor lymphocytes. The phase I portion of the study determined the optimal dose of lymphocytes. Two days after receiving the donor lymphocytes, the patients receive 2 daily doses of cyclophosphamide. One day after receiving cyclophosphamide, the patients receive stem cell from their donor. Tacrolimus and mycophenylate mofetil are used as GVHD prophylaxis.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00429143
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Neal Flomenberg, MD||Thomas Jefferson University|