Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplant (RLI)
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|ClinicalTrials.gov Identifier: NCT00909948|
Recruitment Status : Terminated (Slow Accrual)
First Posted : May 29, 2009
Last Update Posted : March 29, 2018
The proposed study is based on our observation of paradoxical tumor regression after rejection of the donor graft in conjunction with the results of our murine experiments. We hypothesize that clinically meaningful responses can be achieved in patients with advanced malignancies with a transplant strategy using nonmyeloablative conditioning and related mismatched donor stem cell transplant where the intention will be to initially achieve mixed chimerism which will be followed by recipient lymphocyte infusion (RLI) in an attempt to deliberately reject the donor graft. This will lead to the development of novel transplant strategies for achieving antitumor effects without the risk of graft versus host disease (GVHD). This proposed protocol is a Pilot Study that will evaluate the safety of this outpatient transplant strategy, i.e., establishment of initial mixed chimerism followed by RLI for donor graft rejection, in patients with advanced lymphomas, and multiple myeloma.
In addition, because RLI have been reported to reverse ongoing GVHD, this approach might potentially reverse GVHD while achieving antitumor responses if this complication unexpectedly occurs.
|Condition or disease||Intervention/treatment||Phase|
|Non Hodgkin's Lymphoma Hodgkin Disease Multiple Myeloma||Other: Fludarabine and total body irradiation Radiation: Total body irradiation||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||7 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplant|
|Study Start Date :||November 2008|
|Actual Primary Completion Date :||August 2012|
|Actual Study Completion Date :||August 2012|
Active Comparator: Fludarabine
The patients in this cohort will receive fludarabine 30 mg/m2/day on days -4 to -2 and 200 cGy TBI on day 0.
Other: Fludarabine and total body irradiation
The patients in the second cohort will receive fludarabine 30 mg/m2/day on days -4 to -2 and 200 cGy TBI on day 0.
Active Comparator: TBI only
Patients will be given 200 centiGray (cGy) total body irradiation (TBI) in one fraction. TBI will be given on day 0, 4 to 6 hours prior to HCT.
Radiation: Total body irradiation
Patients will receive 200 cGy TBI on day 0,4-6 hours prior to HCT.
- To determine the safety at ≤100 days of a non myeloablative mismatched related HCT when followed by recipient leukocyte infusion to induce deliberate rejection of the donor graft. [ Time Frame: 100 days post transplant ]
- To evaluate the incidence of acute and chronic GVHD [ Time Frame: Up to 2 years post transplant ]
- To evaluate the incidence of loss of donor grafts [ Time Frame: Up to 2 years post transplant ]
- To evaluate progression-free and overall survival [ Time Frame: Up to 2 years post transplant ]
- To evaluate antitumor responses following this transplant strategy [ Time Frame: Up to 2 years post transplant ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00909948
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Bimalangshu R Dey, MD, PhD||MGH|