Clinical trial NCT00429143
Conditions: Hematologic Malignancies
Keywords: Hematologic Malignancies Two Step Approach Haploidentical Transplant
Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
Start date: 2006-01-01; Completion date: 2010-06-01
Enrollment: 27 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Patients undergoing hematopoietic stem cell transplant from a partially matched related donor
Interventions: intervention 1: Total Body Irradiation (TBI) intervention 2: Donor Lymphocyte Infusion (DLI) intervention 3: Cyclophosphamide (CY) intervention 4: Tacrolimus intervention 5: Mycophenolate Mofetil (MMF) intervention 6: Hematopoietic Stem Cell Transplant (HSCT)
Intervention descriptions: intervention 1: TBI twice daily days 6-9 prior to transplant (HSCT) intervention 2: DLI given 6 days prior to transplant (HSCT). intervention 3: Cyclophosphamide given once daily at 60 mg/kg on days 2 and 3 prior to transplant (HSCT). intervention 4: Tacrolimus given one day prior to transplant (HSCT). intervention 5: MMF given one day prior to transplant (HSCT). intervention 6: CD34+ selected Hematopoietic Stem Cell Transplant (HSCT) is performed. This is the day of transplantation.

Protocol documents: