Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplant (RLI)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00909948 |
Recruitment Status :
Terminated
(Slow Accrual)
First Posted : May 29, 2009
Last Update Posted : March 29, 2018
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |

Arm | Intervention/treatment |
---|---|
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 ]

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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
-
Patients with chemorefractory non-Hodgkin's or Hodgkin's lymphoma or multiple myeloma.
Criteria for consideration of enrollment will include:
- primary refractory or refractory relapsed disease for which autologous HCT is unlikely to be beneficial;
- relapse after autologous HCT
- ineligibility for standard myeloablative or nonmyeloablative allo-HCT because of either lack of a donor or patient considerations
- Non Hodgkin's lymphoma, or Hodgkin's lymphoma: primary refractory or refractory relapse
- Multiple myeloma; primary refractory or refractory relapse
- Patients with the above malignancies who have had a previous autologous or allogeneic bone marrow or stem cell transplant.
- An estimated disease-free survival of less than one year.
- Age 18 to age < 75 years
- ECOG performance status of 0, 1, or 2.
Exclusion Criteria:
- Patients whose life expectancy is limited by diseases other than their malignancy
- Patients who have a 5/6 or better matched related donor or a 4/6 or better umbilical cord blood donor and who are medically eligible for conventional myeloablative or non-myeloablative transplant will be excluded
- Cardiac disease: symptomatic congestive heart failure or RVG or echocardiogram determined LVEF ogf< 30%, active angina pectoris or uncontrolled hypertension
- Pulmonary disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or corrected DLCO < 40% of predicted
- Renal disease: serum creatinine > 3.0 mg/dl.
- Hepatic disease: serum bilirubin > 3.0 mg/dl or alkaline phosphatase, SGOT or SGPT > 3 x ULN
- Neurologic disease: symptomatic leukoencephalopathy, active CNS malignancy or other neuropsychiatric abnormalities believed to preclude transplantation (pervious CNS malignancy presently in CR is not an exclusion)
- Uncontrolled infection.
- Recipient leukocyte infusion (RLI) might involve the infusion of circulating tumor cells to the patients. To minimize this risk patients who have evidence of circulating tumor cells by light microscopy and flow cytometry will be excluded
- Patients with acute leukemia will be excluded because they will likely have much greater circulating tumor burden, which would increase the risk of infusion of clonal tumor cells

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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 |
Responsible Party: | Bimalangshu Dey, MD, Massachusetts General Hospital |
ClinicalTrials.gov Identifier: | NCT00909948 |
Obsolete Identifiers: | NCT00981760 |
Other Study ID Numbers: |
Protocol 07-068 |
First Posted: | May 29, 2009 Key Record Dates |
Last Update Posted: | March 29, 2018 |
Last Verified: | March 2018 |
Related stem cell transplant, TBI, Mismatched stem cell transplant Fludarabine |
Non-myeloablative Lymphoma Multiple myeloma |
Multiple Myeloma Hodgkin Disease Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms, Plasma Cell |
Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Fludarabine Antineoplastic Agents |