Trial record 1 of 1 for:    NCT01457885
Previous Study | Return to List | Next Study

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

This study is currently recruiting participants.
Verified July 2013 by University of Michigan Cancer Center
Sponsor:
Collaborators:
Genzyme, a Sanofi Company
Otsuka Pharmaceutical Development & Commercialization, Inc.
Information provided by (Responsible Party):
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT01457885
First received: October 19, 2011
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Acute Myeloblastic Leukemia
Drug: Clofarabine/Busulfan x 4
Procedure: Peripheral blood stem cell transplant
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Multi-center Single Arm Phase II Study of Myeloablative Allogeneic Stem Cell Transplantation for Non-remission Acute Myeloblastic Leukemia (AML) Using Clofarabine and Busulfan x 4 (CloBu4) Regimen

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:
  • Disease free survival following transplant using a CloBu4 conditioning regimen for patients with non-remission AML [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival following transplant using a CloBu4 conditioning regimen for patients with non-remission AML [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 75
Study Start Date: November 2011
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CloBu4 regimen
After pre-conditioning with CloBu4 (Clofarabine/Busulfan x 4), subjects will receive a peripheral blood stem cell transplant
Drug: 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
Procedure: Peripheral blood stem cell transplant
Peripheral blood stem cell transplant, after pre-conditioning drug treatment

  Eligibility

Ages Eligible for Study:   2 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01457885

Locations
United States, Alabama
University of Alabama, Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Shin Mineishi, MD       shin.mineishi@ccc.uab.edu   
Principal Investigator: Shin Mineishi, MD         
United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Samer Khaled, MD    626-256-4673      
Contact: Mei Cheung    (626) 256-4673 (ext. 60078)    mcheung@coh.org   
Principal Investigator: Samer Khaled, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Joseph McGuirk, DO    913-588-6029      
Principal Investigator: Joseph McGuirk, DO         
United States, Michigan
University of Michigan Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: John M Magenau, MD    734-936-8785    johnmage@med.umich.edu   
Principal Investigator: John M Magenau, MD         
United States, Missouri
Washington University at St Louis Recruiting
St Louis, Missouri, United States, 63110
Contact: Peter Westervelt, MD    314-454-8333      
Principal Investigator: Peter Westervelt, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Scott Rowley, M.D.    551-996-8297      
Principal Investigator: Scott Rowley, M.D.         
United States, Pennsylvania
University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Noelle Frey, MD    215-662-6901    noelle.frey@uphs.upenn.edu   
Principal Investigator: Noelle Frey, MD         
United States, Tennessee
Vanderbuilt University Recruiting
Nashville, Tennessee, United States, 37232
Contact: Madan Jagasia, MD    615-936-1803    madan.jagasia@vanderbilt.edu   
Principal Investigator: Madan Jagasia, MD         
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98109
Contact: Pam Becker, MD    206-288-7222    pbecker@seattlecca.org   
Principal Investigator: Pam Becker, MD         
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Hari Parameswaran, MD    414-805-6800    phari@mcw.edu   
Principal Investigator: Hari Parameswaran, MD         
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G 1X8
Contact: Tali Schechter-Finkelstein, MD    (416) 813-7645 ext 4505    tal.schechter-finkelstein@sickkids.ca   
Principal Investigator: Talia Schechter-Finkelstein, MD         
Princess Margaret Hospital Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Dennis Kim, MD    (416) 946-4501 ext 2464    dennis.kim@uhn.ca   
Principal Investigator: Dennis Kim, MD         
Sponsors and Collaborators
University of Michigan Cancer Center
Genzyme, a Sanofi Company
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Chair: Shin Mineishi, MD University of Alabama at Birmingham
Principal Investigator: John M Magenau, MD University of Michigan, Department of Internal Medicine
Study Chair: Stephen J Forman, MD City of Hope National Medical Center
  More Information

No publications provided

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT01457885     History of Changes
Other Study ID Numbers: UMCC 2011.038
Study First Received: October 19, 2011
Last Updated: July 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:
AML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Busulfan
Clofarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists

ClinicalTrials.gov processed this record on April 17, 2014