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

NCT01457885 | Completed Phase 2 Results DMC

• 1 other identifier: UMCC 2011.038
• Study Type: interventional
• Target: 75
• Locations: 2 countries
• Sites: 12

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

Keywords

AML

Outcome Measures

Primary Outcomes (1)

• Cumulative Incidence of Non Relapse Mortality (NRM)

  Percentage of patients passed without relapse/recurrence at 1 year.

  1 year

Secondary Outcomes (2)

• The Percentage of Patients Alive at 1 Year

  1 year

• Incidence of Relapse

  2 years

Study Arms (1)

CloBu4 regimen

EXPERIMENTAL

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

Drug: Clofarabine/Busulfan x 4; Procedure: Peripheral blood stem cell transplant

Interventions

Clofarabine/Busulfan x 4 DRUG

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

CloBu4 regimen

Peripheral blood stem cell transplant PROCEDURE

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

CloBu4 regimen

Eligibility Criteria

• Age: 2 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Genzyme, a Sanofi Company: collaborator
• Otsuka Pharmaceutical Development & Commercialization, Inc.: collaborator

Study Sites (12)

University of Alabama, Birmingham

Birmingham, Alabama, 35233, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Washington University at St Louis

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbuilt University

Nashville, Tennessee, 37232, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Clofarabine; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. John Magenau, M.D.
• Organization: University of Michigan Comprehensive Cancer Center

johnmage@umich.edu

734-936-8785

Study Officials

• Shin Mineishi, MD

  University of Alabama at Birmingham

  STUDY CHAIR

• John M Magenau, MD

  University of Michigan, Department of Internal Medicine

  PRINCIPAL INVESTIGATOR

• Stephen J Forman, MD

  City of Hope National Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: October 19, 2011
• First Posted: October 24, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2014
• Study Completion: June 14, 2016
• Last Updated: June 2, 2017
• Results First Posted: July 25, 2016

Record last verified: 2017-05

Locations

CA (2); US (10)