Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen

NCT ID: NCT01457885

Last Updated: 2017-06-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2016-06-14

Brief Summary

Although transplant results for AML in complete remission (CR) at the time of transplant have improved, transplant results for non-remission AML have been quite poor. Most multi-center studies have focused on standard risk AML patients and not many studies have been done in this population of patients with non-remission AML. There are a large number of older patients with non-remission AML because the complete remission rate with induction chemotherapy decreases with age. Such older patients do not tolerate conventional full intensity conditioning regimens. Thus, an effective and tolerable conditioning regimen for non-remission AML is a great unmet need for current transplant practice.

From the investigators earlier study, it is suggested that replacing Fludarabine of standard FluBu4 regimen by Clofarabine (a related drug with much more potent anti-leukemia effect) in the transplant conditioning regimen may potentiate the anti-tumor activity of the conditioning regimen without adding significant toxicity, a goal of new conditioning regimen development.

The investigators expect to enroll a total of 75 patients from about fifteen sites. The investigators main objective is to confirm both the safety and efficacy as measured by one-year overall survival, of the CloBu4 combination as full intensity conditioning for non-remission acute myelogenous leukemia.

Conditions

Acute Myeloblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CloBu4 regimen

After pre-conditioning with CloBu4 (Clofarabine/Busulfan x 4), subjects will receive a peripheral blood stem cell transplant

Group Type: EXPERIMENTAL

Clofarabine/Busulfan x 4

Intervention Type: DRUG

• Clofarabine IV dose level: 40 mg/m2/day x 5 days
• Busulfan IV dose level: 3.2 mg/kg daily x 4 days

Peripheral blood stem cell transplant

Intervention Type: PROCEDURE

Peripheral blood stem cell transplant, after pre-conditioning drug treatment

Interventions

Clofarabine/Busulfan x 4

• Clofarabine IV dose level: 40 mg/m2/day x 5 days
• Busulfan IV dose level: 3.2 mg/kg daily x 4 days

Intervention Type: DRUG

Peripheral blood stem cell transplant

Peripheral blood stem cell transplant, after pre-conditioning drug treatment

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

Disease Criteria

• AML not in remission at the time of transplant

• "Not in remission" is defined as "greater than 5.0% bone marrow blasts by aspirate morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration.
• For primary induction failure patients: Patients must have failed at least 2 induction regimens.
• For patients with relapsed disease: Patients who relapse more than 6 months after preceding remission must fail at least one reinduction regimen to be eligible. For patients in whom the preceding remission is equal to or shorter than 6 months duration, no re-induction regimen is required to qualify for this protocol.
• If the pre-transplant bone marrow aspirate and biopsy are hypoplastic (less than 10% cellularity), and blast percentages cannot be determined, the patient is eligible if the preceding bone marrow met the above criteria.
• Patients with peripheral circulating blasts or patients with extramedullary leukemia are eligible if bone marrow aspirate and biopsy meets the above criteria. Age and Organ Function Criteria
• Age: 2 to 65 years in age.
• Cardiac: LVEF ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram.
• Pulmonary: FEV1 and FVC capacity) ≥ 40% predicted, DLCO (corrected for hemoglobin) ≥ 40% of predicted.
• Children who are unable to cooperate for pulmonary function tests (PFTs), must have no evidence of dyspnea at rest, no exercise intolerance, and not require supplemental oxygen therapy.
• Renal: Age equal to or older than 12: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula. Age younger than 12: Either estimated or measured CrCl should be greater than 90 ml/min/1.73m2. For estimation, Schwartz formula will be used.
• Hepatic: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); (AST)/ ALT ≤ 2.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN
• Performance status: Karnofsky ≥ 70%., or Lansky≥70% Consent: All patients must sign informed consent

Exclusion Criteria

• Active life-threatening cancer requiring treatment other than AML
• Non-compliant to medications.
• No appropriate caregivers identified.
• HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive
• Active life-threatening cancer requiring treatment other than AML
• Uncontrolled medical or psychiatric disorders.
• Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection
• Active central nervous system (CNS) leukemia
• Preceding allogeneic HSCT
• Receiving intensive chemotherapy within 21 days of registration.
• Patients with preceding primary myelofibrosis
• Peripheral blasts > 10,000/μL at the time of registration

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: collaborator

University of Michigan Rogel Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shin Mineishi, MD

Role: STUDY_CHAIR

University of Alabama at Birmingham

John M Magenau, MD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan, Department of Internal Medicine

Stephen J Forman, MD

Role: STUDY_CHAIR

City of Hope National Medical Center

Locations

University of Alabama, Birmingham

Birmingham, Alabama, United States

City of Hope National Medical Center

Duarte, California, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Washington University at St Louis

St Louis, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Vanderbuilt University

Nashville, Tennessee, United States

University of Washington

Seattle, Washington, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Hospital for Sick Children

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

UMCC 2011.038

Identifier Type: -

Identifier Source: org_study_id