Intentional Rejection of the Donor Graft Using Recipient Leukocyte Infusion(s) Following Nonmyeloablative Allogeneic Stem Cell Transplant
NCT ID: NCT00909948
Last Updated: 2018-03-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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TERMINATED
PHASE1
7 participants
INTERVENTIONAL
2008-11-30
2012-08-31
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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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.
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.
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.
Total body irradiation
Patients will receive 200 cGy TBI on day 0,4-6 hours prior to HCT.
Interventions
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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.
Total body irradiation
Patients will receive 200 cGy TBI on day 0,4-6 hours prior to HCT.
Eligibility Criteria
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Inclusion Criteria
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
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
18 Years
75 Years
ALL
No
Sponsors
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Massachusetts General Hospital
OTHER
Responsible Party
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Bimalangshu Dey
MD
Principal Investigators
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Bimalangshu R Dey, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
MGH
Locations
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Massachusetts General Hospital
Boston, Massachusetts, United States
Countries
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References
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Bortin MM, Rimm AA, Saltzstein EC. Graft versus leukemia: quantification of adoptive immunotherapy in murine leukemia. Science. 1973 Feb 23;179(4075):811-3. doi: 10.1126/science.179.4075.811.
Hill GR, Krenger W, Ferrara JL. The role of cytokines in acute graft-versus-host disease. Cytokines Cell Mol Ther. 1997 Dec;3(4):257-66.
Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N, Sachs DH, Sykes M, Spitzer TR. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biol Blood Marrow Transplant. 2003 May;9(5):320-9. doi: 10.1016/s1083-8791(03)00077-6.
Sykes M, Romick ML, Sachs DH. Interleukin 2 prevents graft-versus-host disease while preserving the graft-versus-leukemia effect of allogeneic T cells. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5633-7. doi: 10.1073/pnas.87.15.5633.
Mapara MY, Kim YM, Wang SP, Bronson R, Sachs DH, Sykes M. Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells. Blood. 2002 Sep 1;100(5):1903-9. doi: 10.1182/blood-2002-01-0023.
Kraus AB, Shaffer J, Toh HC, Preffer F, Dombkowski D, Saidman S, Colby C, George R, McAfee S, Sackstein R, Dey B, Spitzer TR, Sykes M. Early host CD8 T-cell recovery and sensitized anti-donor interleukin-2-producing and cytotoxic T-cell responses associated with marrow graft rejection following nonmyeloablative allogeneic bone marrow transplantation. Exp Hematol. 2003 Jul;31(7):609-21. doi: 10.1016/s0301-472x(03)00082-1.
Spitzer TR, McAfee S, Sackstein R, Colby C, Toh HC, Multani P, Saidman S, Weyouth DW, Preffer F, Poliquin C, Foley A, Cox B, Andrews D, Sachs DH, Sykes M. Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies. Biol Blood Marrow Transplant. 2000;6(3A):309-20. doi: 10.1016/s1083-8791(00)70056-5.
Rubio MT, Kim YM, Sachs T, Mapara M, Zhao G, Sykes M. Antitumor effect of donor marrow graft rejection induced by recipient leukocyte infusions in mixed chimeras prepared with nonmyeloablative conditioning: critical role for recipient-derived IFN-gamma. Blood. 2003 Sep 15;102(6):2300-7. doi: 10.1182/blood-2002-12-3949. Epub 2003 Jun 5.
Ballen KK, Becker PS, Emmons RV, Fitzgerald TJ, Hsieh CC, Liu Q, Heyes C, Clark Y, Levy W, Lambert JF, Chiafari F, Szymanski I, Rososhansky S, Popovsky MA, Stewart FM, Quesenberry PJ. Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. Blood. 2002 Jul 15;100(2):442-50. doi: 10.1182/blood.v100.2.442.
Colby C, Sykes M, Sachs DH, Spitzer TR. Cellular modulation of acute graft-vs.-host disease. Biol Blood Marrow Transplant. 1997 Dec;3(6):287-93.
Other Identifiers
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Protocol 07-068
Identifier Type: -
Identifier Source: org_study_id
NCT00981760
Identifier Type: -
Identifier Source: nct_alias
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