Acute Myeloid Leukemia T Cell Depletion to Improve Transplants in Adults With Acute Myeloid Leukemia (BMT CTN 0303)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2012 by National Heart, Lung, and Blood Institute (NHLBI).
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00201240
First received: September 16, 2005
Last updated: January 12, 2012
Last verified: January 2012
  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)

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00201240

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
Sponsors and Collaborators
Blood and Marrow Transplant Clinical Trials Network
Investigators
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 April 14, 2014