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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00201240
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : November 10, 2014
Last Update Posted : September 25, 2017
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary:

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 or disease Intervention/treatment Phase
Leukemia, Myelocytic, Acute Biological: CD34+ selection with CliniMACS device Phase 2

Detailed Description:


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.


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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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)
Study Start Date : June 2005
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Arm Intervention/treatment
Experimental: CD34+ selection with CliniMACS device
T cell depletion using Miltenyi device
Biological: CD34+ selection with CliniMACS device
CD34+ cell selection will be performed according to procedures given in the CliniMACS Users Operating Manual and institutional Standard Operating Procedures (SOPs) in place and validated at the study sites. CliniMACS (Miltenyi device) to target CD34+ >5 x 10*6/kg and CD3+ < 1 x 10*5/kg
Other Name: T Cell Depletion

Primary Outcome Measures :
  1. 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 ]
    The primary analysis will consist of estimating the 6-month DFS (from day of enrollment) probability based on the Kaplan-Meier product limit estimator. The 6-month DFS probability and confidence interval will be calculated. All registered patients will be considered for this analysis.

Secondary Outcome Measures :
  1. Leukemia Relapse [ Time Frame: Months 12 and 36 ]
    To assess the incidence of acute leukemia relapse from day of transplant, a cumulative incidence curve will be computed along with a 95% confidence interval. Death prior to relapse will be considered as a competing risk.

  2. Neutrophil Engraftment [ Time Frame: 28 day ]
    Time to neutrophil engraftment is measured by determining the first of three consecutive measurements of absolute neutrophil count ≥ 500/uL following conditioning regimen induced nadir, starting from Day 0.

  3. Platelet Engraftment [ Time Frame: 6 Months ]
    Time to platelet engraftment is measured by determining the first of three consecutive measurements of platelet count ≥ 20,000/uL without platelet transfusion support for seven days, starting from Day 0.

  4. Graft Failure [ Time Frame: Day 100 ]
    Primary graft failure is defined as the failure to achieve an ANC > 500 cells/µL by Day +30. Secondary graft failure is defined as initial neutrophil engraftment followed by subsequent decline in neutrophil counts < 500 cells/µL, unresponsive to growth factor therapy.

  5. Acute Graft Versus Host Disease (GVHD) [ Time Frame: Day 100 ]
    Incidence and severity of acute GVHD will be graded according to the BMT CTN MOP.

  6. Chronic Graft Versus Host Disease (GVHD) [ Time Frame: Year 2 ]
    Incidence and severity of chronic GVHD will be scored according to the BMT CTN MOP.

  7. Transplant Related Mortality [ Time Frame: Months 12, 24, and 36 ]
    Death occurring in a patient in continuing complete remission.

  8. Determination of Infusional Toxicity [ Time Frame: 28 day ]
  9. Disease-free Survival (DFS) [ Time Frame: Months 6, 12, and 36 ]
    DFS is defined as the minimum time interval of times to relapse/recurrence, to death or to the last follow-up, from the time of transplant.

  10. Overall Survival [ Time Frame: Months 12 and 36 ]
    Overall survival is defined as time from transplant to death or last follow-up.

  11. CD34+ and CD3+ Cell Doses [ Time Frame: Day 0 ]
    Total CD34+ and CD3+ cell doses will be calculated based on results of flow cytometric analysis.

  12. Post-transplant Lymphoproliferative Disorder (PTLD) [ Time Frame: Year 2 ]
    PTLD is defined as increased Epstein Barr Virus viremia requiring clinical intervention.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
  • Diffusing capacity of the lung for carbon monoxide (DLCO) of at least 40% (corrected for hemoglobin) with no symptomatic pulmonary disease
  • Left ventricular ejection fraction (LVEF) by Multi Gated Acquisition Scan (MUGA) or echocardiogram greater than 40%
  • Serum creatinine greater than 2 mg/dL, bilirubin greater than 2 mg/dL, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00201240

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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, New York
Memorial Sloan-Kettering Cancer Center
New York, 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
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
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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
Additional Information:
Publications of Results:
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Responsible Party: National Heart, Lung, and Blood Institute (NHLBI) Identifier: NCT00201240    
Other Study ID Numbers: BMTCTN0303
U01HL069254 ( U.S. NIH Grant/Contract )
U01HL069249 ( U.S. NIH Grant/Contract )
U01HL069278 ( U.S. NIH Grant/Contract )
U01HL069294 ( U.S. NIH Grant/Contract )
U01HL069315 ( U.S. NIH Grant/Contract )
U01HL069348 ( U.S. NIH Grant/Contract )
284 ( Other Identifier: NHLBI )
First Posted: September 20, 2005    Key Record Dates
Results First Posted: November 10, 2014
Last Update Posted: September 25, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Within 6 months of official study closure at participating sites.
Access Criteria: Available to the public
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type