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

Primary Purpose

Acute Myeloblastic Leukemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Clofarabine/Busulfan x 4
Peripheral blood stem cell transplant
Sponsored by
University of Michigan Rogel Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloblastic Leukemia focused on measuring AML

Eligibility Criteria

2 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama, Birmingham
  • City of Hope National Medical Center
  • University of Kansas Medical Center
  • University of Michigan Cancer Center
  • Washington University at St Louis
  • Hackensack University Medical Center
  • University of Pennsylvania
  • Vanderbuilt University
  • University of Washington
  • Medical College of Wisconsin
  • Hospital for Sick Children
  • Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CloBu4 regimen

Arm Description

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

Outcomes

Primary Outcome Measures

Cumulative Incidence of Non Relapse Mortality (NRM)
Percentage of patients passed without relapse/recurrence at 1 year.

Secondary Outcome Measures

The Percentage of Patients Alive at 1 Year
Overall survival was calculated following transplant using a CloBu4 conditioning regimen for patients with non-remission AML
Incidence of Relapse

Full Information

First Posted
October 19, 2011
Last Updated
May 3, 2017
Sponsor
University of Michigan Rogel Cancer Center
Collaborators
Genzyme, a Sanofi Company, Otsuka Pharmaceutical Development & Commercialization, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01457885
Brief Title
Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen
Acronym
CloBu4
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
June 14, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
Collaborators
Genzyme, a Sanofi Company, Otsuka Pharmaceutical Development & Commercialization, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloblastic Leukemia
Keywords
AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CloBu4 regimen
Arm Type
Experimental
Arm Description
After pre-conditioning with CloBu4 (Clofarabine/Busulfan x 4), subjects will receive a peripheral blood stem cell transplant
Intervention Type
Drug
Intervention Name(s)
Clofarabine/Busulfan x 4
Intervention Description
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
Procedure
Intervention Name(s)
Peripheral blood stem cell transplant
Intervention Description
Peripheral blood stem cell transplant, after pre-conditioning drug treatment
Primary Outcome Measure Information:
Title
Cumulative Incidence of Non Relapse Mortality (NRM)
Description
Percentage of patients passed without relapse/recurrence at 1 year.
Time Frame
1 year
Secondary Outcome Measure Information:
Title
The Percentage of Patients Alive at 1 Year
Description
Overall survival was calculated following transplant using a CloBu4 conditioning regimen for patients with non-remission AML
Time Frame
1 year
Title
Incidence of Relapse
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shin Mineishi, MD
Organizational Affiliation
University of Alabama at Birmingham
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
John M Magenau, MD
Organizational Affiliation
University of Michigan, Department of Internal Medicine
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephen J Forman, MD
Organizational Affiliation
City of Hope National Medical Center
Official's Role
Study Chair
Facility Information:
Facility Name
University of Alabama, Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Michigan Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Washington University at St Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Vanderbuilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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