Acute Myeloid Leukemia T Cell Depletion to Improve Transplants in Adults With Acute Myeloid Leukemia (BMT CTN 0303)
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Purpose
This study is a single arm Phase II, multicenter trial. It is designed to determine whether the anticipated endpoints for a T cell depleted transplant arm of a planned prospective randomized trial comparing T cell depleted and unmodified hematopoietic allografts are likely to be achieved in a multicenter study conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN or Network). The study population is patients with acute myeloid leukemia (AML) in first or second morphologic complete remission. The enrollment is 45 patients.
Based on published results of unmodified transplants from HLA-matched siblings applied to patients with AML in first or second morphologic complete remission, a significant improvement in results with a graft modified as specified in this protocol would be expected if disease-free survival (DFS) at 6 months was greater than 75%, the true incidence of transplant-related mortality at 1 year was less than 30%, and the DFS rate at 2 years was greater 70% for patients transplanted in first remission and less than 60% for patients transplanted in second remission. Additional secondary endpoints include the following: graft failure rate and incidences of acute grade II-IV and chronic graft-versus-host disease (GVHD). Additionally, the trial will have target specific doses of CD34+ progenitors and CD3+ T cells to be obtained following fractionation with the CliniMACS system. Based on the results of this trial, a Phase III trial comparing T cell depleted peripheral blood stem cell transplants (PBSCT) with unmanipulated bone marrow or unmanipulated PBSCT will be designed.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia, Myelocytic, Acute |
Device: T cell depletion |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Single Arm, Multicenter Phase II Trial of Transplants of HLA-Matched, CD34+ Enriched, T Cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With AML in First or Second Morphologic Complete Remission (BMT CTN #0303) |
- Probability of disease-free survival (DFS) at 6 months post-transplant (death or relapse will be considered events for this endpoint) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
- Leukemia relapse [ Time Frame: 6, 12, and 24 months ] [ Designated as safety issue: No ]
- Neutrophil engraftment [ Time Frame: 28 day ] [ Designated as safety issue: No ]
- Platelet engraftment [ Time Frame: 100 day, 6 months, 1 year ] [ Designated as safety issue: No ]
- Graft failure [ Time Frame: 28 and 100 day ] [ Designated as safety issue: Yes ]
- Acute graft-versus-host disease [ Time Frame: 100 day ] [ Designated as safety issue: Yes ]
- Chronic graft-versus-host disease [ Time Frame: 100 day, 6 months, 1 year ] [ Designated as safety issue: Yes ]
- Transplant related mortality [ Time Frame: 100 day ] [ Designated as safety issue: Yes ]
- Determination of infusional toxicity [ Time Frame: 28 day ] [ Designated as safety issue: Yes ]
- Disease-free survival [ Time Frame: 1 year, 2 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 6 months, 1 year, 2 years ] [ Designated as safety issue: No ]
- CD34+ and CD3+ cell doses [ Time Frame: Day 0 ] [ Designated as safety issue: No ]
- Post-transplant lymphoproliferative disorder (PTLD) [ Time Frame: 6 months, 1 year, 2 years ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 45 |
| Study Start Date: | June 2005 |
| Estimated Study Completion Date: | June 2013 |
| Estimated Primary Completion Date: | January 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: TCD
T cell depletion using Miltenyi device
|
Device: T cell depletion
CliniMACS (Myltenyi device) to target CD34+ >5 x 10*6/kg and CD3+ < 1 x 10*5/kg
|
Detailed Description:
BACKGROUND:
Allogeneic hematopoietic cell transplantation is an accepted therapy for AML. Transplants of unmodified HLA-matched related bone marrow or peripheral blood stem cells following conditioning with total body irradiation (TBI) and cyclophosphamide or VP-16 or busulfan and cyclophosphamide have led to sustained DFS rates of 45-60% for adults transplanted in first complete remission (CR1) and 40-53% for patients transplanted in second complete remission (CR2). In several single center and multicenter cooperative group prospective trials comparing HLA-matched allogeneic transplants to chemotherapy in the treatment of AML in CR1, DFS rates for the transplant arm were almost invariably superior; however, these advantages were statistically significant in only a minority of the cooperative group studies conducted. In each study, the risk of relapse was significantly lower for patients receiving allogeneic transplants. However, this advantage was counterbalanced by transplant-related mortality, principally reflecting infections complicating GVHD and its treatment.
DESIGN NARRATIVE:
Despite increased risks of infection, development of effective T cell depletion (TCD) techniques for prevention of GVHD and tolerable modifications of regimens for pre-transplant cytoreduction that secure consistent engraftment offer the potential for significant decreases in transplant-related mortality. Furthermore, the use of TCD transplants in the treatment of patients with AML is not associated with substantial increases in the incidence of relapse. Several single center trials indicate highly encouraging long-term results, particularly for patients with AML in CR1 or CR2. Although the number of cases in each single center series is limited, the consistency of the results suggests that the use of an effective technique for TCD together with an adequate cytoreductive regimen might yield transplant results superior to those achieved with unmodified grafts.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Patients with AML with or without prior history of myelodysplastic syndrome based on the World Health Organization criteria at the following stages:
- First morphologic complete remission (CR)
- Second morphologic CR
- If prior history of central nervous system (CNS) involvement, no evidence of active CNS leukemia during the pre-transplant evaluation (no evidence of leukemic blasts in cerebrospinal fluid)
- First or second CR was achieved after no more than two cycles of induction (or re-induction for patients in second CR) chemotherapy
- No more than 6 months elapsed from documentation of CR to transplant for patients in first CR, or 3 months for patients in second CR.
- A 6/6 HLA antigen (A, B, DRB1)-compatible sibling donor; the match may be determined at serologic level for HLA-A and HLA-B loci; DRB1 must be matched at least at low-resolution using DNA typing techniques; HLA-C will be typed at the serologic level, but not included in the match algorithm
- Karnofsky performance status greater than 70%
- Life expectancy greater than 8 weeks
- DLCO (diffusing capacity of lungs for carbon monoxide) of at least 40% (corrected for hemoglobin) with no symptomatic pulmonary disease
- LVEF (left ventricular ejection fraction) by MUGA scan or echocardiogram greater than 40%
- Serum creatinine greater than 2 mg/dL, bilirubin greater than 2 mg/dL, and AST and ALT levels at least 3 times the upper limit of normal at time of enrollment
- Willingness of both the patient and the donor to participate
Exclusion Criteria:
- M3-AML (acute promyelocytic leukemia) in first CR
- Acute leukemia following blast transformation of prior chronic myelogenous leukemia (CML) or other myeloproliferative disease
- M4Eo-AML with inv 16 in first CR
- AML with t(8;21) in first CR
- Participation in other clinical trials that involve investigational drugs or devices except with permission from the Medical Monitor
- Evidence of active Hepatitis B or C infection or evidence of cirrhosis
- HIV positive
- Uncontrolled diabetes mellitus
- If proven or probable invasive fungal infection, infection must be controlled; patients may be on prophylactic anti-fungal agents, but are not permitted to be on anti-fungal agents for therapeutic purposes (i.e., active treatment for disease)
- Uncontrolled viral or bacterial infection (currently taking medication without clinical improvement)
- Documented allergy to iron dextran or murine proteins
- Pregnant or breastfeeding; women of childbearing age must avoid becoming pregnant while in the study
- Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)
Contacts and Locations| United States, California | |
| City of Hope National Medical Center | |
| Duarte, California, United States, 91010 | |
| University of California, San Francisco | |
| San Francisco, California, United States, 94143 | |
| United States, Massachusetts | |
| Dana Farber Cancer Institute/Brigham & Women's Hospital | |
| Boston, Massachusetts, United States, 02114 | |
| United States, Missouri | |
| Washington University/Barnes Jewish Hospital | |
| St. Louis, Missouri, United States, 63110 | |
| United States, New York | |
| Memorial Sloan-Kettering Cancer Center | |
| New York City, New York, United States, 10021 | |
| United States, Ohio | |
| University Hospitals of Cleveland/Case Western | |
| Cleveland, Ohio, United States, 44106 | |
| Ohio State/Arthur G. James Cancer Hospital | |
| Columbus, Ohio, United States, 43210 | |
| United States, Pennsylvania | |
| University of Pennsylvania Cancer Center | |
| Philadelphia, Pennsylvania, United States, 19104 | |
| United States, Wisconsin | |
| Medical College of Wisconsin | |
| Milwaukee, Wisconsin, United States, 53211 | |
| Study Chair: | Steven Devine, MD | Ohio State/Arthur G. James Cancer Hospital |
| Principal Investigator: | Parameswaran Hari, MD | Medical College of Wisconsin |
| Principal Investigator: | Hillard Lazarus, MD | University Hospitals of Cleveland/Case Western |
| Principal Investigator: | Lloyd Damon, MD | University of California, San Francisco |
| Study Chair: | Richard O'Reilly, MD | Memorial Sloan-Kettering Cancer Center |
| Principal Investigator: | Robert Soiffer, MD | Dana Farber Cancer Institute/Brigham & Women's Hospital |
| Principal Investigator: | Anthony Stein, MD | City of Hope National Medical Center |
| Principal Investigator: | John DiPersio, MD, PhD | Washington University/Barnes Jewish Hospital |
| Principal Investigator: | Edward Stadtmauer, MD | University of Pennsylvania |
More Information
Additional Information:
No publications provided
| Responsible Party: | National Heart, Lung, and Blood Institute (NHLBI) |
| ClinicalTrials.gov Identifier: | NCT00201240 History of Changes |
| Other Study ID Numbers: | 284, U01 HL069254, U01 HL69249, U01 HL69278, U01 HL69294, U01 HL69315, U01 HL69348 |
| Study First Received: | September 16, 2005 |
| Last Updated: | January 12, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms |
ClinicalTrials.gov processed this record on May 16, 2013