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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. Identifier: NCT00909948
Recruitment Status : Terminated (Slow Accrual)
First Posted : May 29, 2009
Last Update Posted : March 29, 2018
Information provided by (Responsible Party):
Bimalangshu Dey, Massachusetts General Hospital

Brief Summary:

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

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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.

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. To evaluate the incidence of acute and chronic GVHD [ Time Frame: Up to 2 years post transplant ]
  2. To evaluate the incidence of loss of donor grafts [ Time Frame: Up to 2 years post transplant ]
  3. To evaluate progression-free and overall survival [ Time Frame: Up to 2 years post transplant ]
  4. To evaluate antitumor responses following this transplant strategy [ Time Frame: Up to 2 years post transplant ]

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with chemorefractory non-Hodgkin's or Hodgkin's lymphoma or multiple myeloma.

    Criteria for consideration of enrollment will include:

    1. primary refractory or refractory relapsed disease for which autologous HCT is unlikely to be beneficial;
    2. relapse after autologous HCT
    3. ineligibility for standard myeloablative or nonmyeloablative allo-HCT because of either lack of a donor or patient considerations
  2. Non Hodgkin's lymphoma, or Hodgkin's lymphoma: primary refractory or refractory relapse
  3. Multiple myeloma; primary refractory or refractory relapse
  4. Patients with the above malignancies who have had a previous autologous or allogeneic bone marrow or stem cell transplant.
  5. An estimated disease-free survival of less than one year.
  6. Age 18 to age < 75 years
  7. ECOG performance status of 0, 1, or 2.

Exclusion Criteria:

  1. Patients whose life expectancy is limited by diseases other than their malignancy
  2. 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
  3. Cardiac disease: symptomatic congestive heart failure or RVG or echocardiogram determined LVEF ogf< 30%, active angina pectoris or uncontrolled hypertension
  4. Pulmonary disease: severe chronic obstructive lung disease, or symptomatic restrictive lung disease, or corrected DLCO < 40% of predicted
  5. Renal disease: serum creatinine > 3.0 mg/dl.
  6. Hepatic disease: serum bilirubin > 3.0 mg/dl or alkaline phosphatase, SGOT or SGPT > 3 x ULN
  7. 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)
  8. Uncontrolled infection.
  9. 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
  10. 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

Information from the National Library of Medicine

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 identifier (NCT number): NCT00909948

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United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
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Principal Investigator: Bimalangshu R Dey, MD, PhD MGH

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Responsible Party: Bimalangshu Dey, MD, Massachusetts General Hospital 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
Keywords provided by Bimalangshu Dey, Massachusetts General Hospital:
Related stem cell transplant,
Mismatched stem cell transplant
Multiple myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Hodgkin Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Antineoplastic Agents