Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplant (RLI)

This study has suspended participant recruitment.
(Temprorary closure to new accrual because the Baxter Isolex was withdrawn. Will reopen when new device is available.)
Sponsor:
Collaborator:
Information provided by:
Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00909948
First received: May 27, 2009
Last updated: July 21, 2010
Last verified: July 2010
  Purpose

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 Intervention Phase
Non Hodgkin's Lymphoma
Hodgkins Disease.
Multiple Myeloma
Other: Fludarabine and total body irradiation
Radiation: Total body irradiation
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplant

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the incidence of acute and chronic GVHD [ Time Frame: Up to 2 years post transplant ] [ Designated as safety issue: Yes ]
  • To evaluate the incidence of loss of donor grafts [ Time Frame: Up to 2 years post transplant ] [ Designated as safety issue: Yes ]
  • To evaluate progression-free and overall survival [ Time Frame: Up to 2 years post transplant ] [ Designated as safety issue: Yes ]
  • To evaluate antitumor responses following this transplant strategy [ Time Frame: Up to 2 years post transplant ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: November 2008
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00909948

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

Publications:

Responsible Party: Bimalangshu Dey; MD, PhD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00909948     History of Changes
Other Study ID Numbers: Protocol 07-068
Study First Received: May 27, 2009
Last Updated: July 21, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Related stem cell transplant,
TBI,
Mismatched stem cell transplant
Fludarabine
Non-myeloablative
Lymphoma
Multiple myeloma

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Fludarabine
Fludarabine monophosphate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 22, 2014