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

NCT00201240 | Completed Phase 2 Results DMC

• 8 other identifiers: BMTCTN0303U01HL069254U01HL069249U01HL069278U01HL069294U01HL069315U01HL069348284
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 8

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.

Conditions

Leukemia, Myelocytic, Acute

Outcome Measures

Primary Outcomes (1)

• Probability of Disease-free Survival (DFS) at 6 Months Post-transplant (Death or Relapse Will be Considered Events for This Endpoint)

  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.

  6 months

Secondary Outcomes (12)

• Leukemia Relapse

  Months 12 and 36

• Neutrophil Engraftment

  28 day

• Platelet Engraftment

  6 Months

• Graft Failure

  Day 100

• Acute Graft Versus Host Disease (GVHD)

  Day 100

Study Arms (1)

CD34+ selection with CliniMACS device

EXPERIMENTAL

T cell depletion using Miltenyi device

Biological: CD34+ selection with CliniMACS device

Interventions

CD34+ selection with CliniMACS device 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

Also known as: T Cell Depletion

CD34+ selection with CliniMACS device

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (8)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Dana Farber Cancer Institute/Brigham & Women's Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, 44106, United States

Location

Ohio State/Arthur G. James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (3)

• 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.

  PMID: 21875505 RESULT

• 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.

  PMID: 21320619 RESULT

• 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.

  PMID: 22869882 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Adam Mendizabal, PhD
• Organization: The Emmes Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Steven Devine, MD

  Ohio State/Arthur G. James Cancer Hospital

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

• Richard O'Reilly, MD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2005
• First Posted: September 20, 2005
• Study Start: June 1, 2005
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: November 1, 2021
• Results First Posted: November 10, 2014

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public

Locations

US (8)