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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Ontario
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital for Sick Children
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama, Birmingham
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Cancer Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University at St Louis
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbuilt University
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CloBu4 regimen
After pre-conditioning with CloBu4 (Clofarabine/Busulfan x 4), subjects will receive a peripheral blood stem cell transplant
Peripheral blood stem cell transplant, after pre-conditioning drug treatment
  • Clofarabine IV dose level: 40 mg/m2/day x 5 days
  • Busulfan IV dose level: 3.2 mg/kg daily x 4 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative Incidence of Non Relapse Mortality (NRM)
Time Frame: 1 year
Percentage of patients passed without relapse/recurrence at 1 year.
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Patients Alive at 1 Year
Time Frame: 1 year
Overall survival was calculated following transplant using a CloBu4 conditioning regimen for patients with non-remission AML
1 year
Incidence of Relapse
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2011

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

June 14, 2016

Study Registration Dates

First Submitted

October 19, 2011

First Submitted That Met QC Criteria

October 21, 2011

First Posted (Estimate)

October 24, 2011

Study Record Updates

Last Update Posted (Actual)

June 2, 2017

Last Update Submitted That Met QC Criteria

May 3, 2017

Last Verified

May 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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