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

This study is currently recruiting participants. (see Contacts and Locations)
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

October 19, 2011
July 18, 2013
November 2011
September 2015   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT01457885 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Overall survival following transplant using a CloBu4 conditioning regimen for patients with non-remission AML [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Regimen related toxicities [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Time to neutrophil and platelet engraftment [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Incidence and Severity of acute Graft versus Host Disease [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Incidence and Severity of chronic Graft versus Host Disease [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Relapse Rate [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Genomic Instability Analysis at the time of transplant [ Time Frame: At transplant ] [ Designated as safety issue: No ]
  • Genomic Instability Analysis at Relapse [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen
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

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Myeloblastic Leukemia
  • 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
Experimental: CloBu4 regimen
After pre-conditioning with CloBu4 (Clofarabine/Busulfan x 4), subjects will receive a peripheral blood stem cell transplant
Interventions:
  • Drug: Clofarabine/Busulfan x 4
  • Procedure: Peripheral blood stem cell transplant
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
75
March 2017
September 2015   (final data collection date for primary outcome measure)

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
Both
2 Years to 65 Years
No
United States,   Canada
 
NCT01457885
UMCC 2011.038
Yes
University of Michigan Cancer Center
University of Michigan Cancer Center
  • Genzyme, a Sanofi Company
  • Otsuka Pharmaceutical Development & Commercialization, Inc.
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
University of Michigan Cancer Center
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP