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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

47 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-06-30

Study Completion Date

2013-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Leukemia, Myelocytic, Acute

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CD34+ selection with CliniMACS device

T cell depletion using Miltenyi device

Group Type EXPERIMENTAL

CD34+ selection with CliniMACS device

Intervention Type BIOLOGICAL

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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

Intervention Type BIOLOGICAL

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

T Cell Depletion

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)

Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Steven Devine, MD

Role: STUDY_CHAIR

Ohio State/Arthur G. James Cancer Hospital

Parameswaran Hari, MD

Role: PRINCIPAL_INVESTIGATOR

Medical College of Wisconsin

Hillard Lazarus, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals of Cleveland/Case Western

Lloyd Damon, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Richard O'Reilly, MD

Role: STUDY_CHAIR

Memorial Sloan Kettering Cancer Center

Robert Soiffer, MD

Role: PRINCIPAL_INVESTIGATOR

Dana Farber Cancer Institute/Brigham & Women's Hospital

Anthony Stein, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope National Medical Center

John DiPersio, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University/Barnes Jewish Hospital

Edward Stadtmauer, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

City of Hope National Medical Center

Duarte, California, United States

Site Status

University of California, San Francisco

San Francisco, California, United States

Site Status

Dana Farber Cancer Institute/Brigham & Women's Hospital

Boston, Massachusetts, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, United States

Site Status

Ohio State/Arthur G. James Cancer Hospital

Columbus, Ohio, United States

Site Status

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

Keever-Taylor CA, Devine SM, Soiffer RJ, Mendizabal A, Carter S, Pasquini MC, Hari PN, Stein A, Lazarus HM, Linker C, Goldstein SC, Stadtmauer EA, O'Reilly RJ. Characteristics of CliniMACS(R) System CD34-enriched T cell-depleted grafts in a multicenter trial for acute myeloid leukemia-Blood and Marrow Transplant Clinical Trials Network (BMT CTN) protocol 0303. Biol Blood Marrow Transplant. 2012 May;18(5):690-7. doi: 10.1016/j.bbmt.2011.08.017. Epub 2011 Aug 26.

Reference Type RESULT

PMID: 21875505 (View on PubMed)

Devine SM, Carter S, Soiffer RJ, Pasquini MC, Hari PN, Stein A, Lazarus HM, Linker C, Stadtmauer EA, Alyea EP 3rd, Keever-Taylor CA, O'Reilly RJ. Low risk of chronic graft-versus-host disease and relapse associated with T cell-depleted peripheral blood stem cell transplantation for acute myelogenous leukemia in first remission: results of the blood and marrow transplant clinical trials network protocol 0303. Biol Blood Marrow Transplant. 2011 Sep;17(9):1343-51. doi: 10.1016/j.bbmt.2011.02.002. Epub 2011 Feb 12.

Reference Type RESULT

PMID: 21320619 (View on PubMed)

Pasquini MC, Devine S, Mendizabal A, Baden LR, Wingard JR, Lazarus HM, Appelbaum FR, Keever-Taylor CA, Horowitz MM, Carter S, O'Reilly RJ, Soiffer RJ. Comparative outcomes of donor graft CD34+ selection and immune suppressive therapy as graft-versus-host disease prophylaxis for patients with acute myeloid leukemia in complete remission undergoing HLA-matched sibling allogeneic hematopoietic cell transplantation. J Clin Oncol. 2012 Sep 10;30(26):3194-201. doi: 10.1200/JCO.2012.41.7071. Epub 2012 Aug 6.

Reference Type RESULT

PMID: 22869882 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document