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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
Sponsor:
Information provided by (Responsible Party):
Bimalangshu Dey, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE May 27, 2009
First Posted Date  ICMJE May 29, 2009
Last Update Posted Date March 29, 2018
Study Start Date  ICMJE November 2008
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2009)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2009)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplant
Official Title  ICMJE Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplant
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non Hodgkin's Lymphoma
  • Hodgkin Disease
  • Multiple Myeloma
Intervention  ICMJE
  • 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.
  • Radiation: Total body irradiation
    Patients will receive 200 cGy TBI on day 0,4-6 hours prior to HCT.
Study Arms  ICMJE
  • 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.
    Intervention: Other: Fludarabine and total body irradiation
  • 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.
    Intervention: Radiation: Total body irradiation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: March 26, 2018)
7
Original Estimated Enrollment  ICMJE
 (submitted: May 28, 2009)
20
Actual Study Completion Date  ICMJE August 2012
Actual Primary Completion Date August 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00909948
Other Study ID Numbers  ICMJE Protocol 07-068
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bimalangshu Dey, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bimalangshu R Dey, MD, PhD MGH
PRS Account Massachusetts General Hospital
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP