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

Phase 2

Completed

Conditions: Acute Myeloblastic Leukemia

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

Registration Number: NCT01457885

Lead Sponsor: University of Michigan Rogel Cancer Center

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 75

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (12): Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
University of Alabama, Birmingham
🇺🇸
Birmingham, Alabama, United States
University of Michigan Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
University of Washington
🇺🇸
Seattle, Washington, United States
Vanderbuilt University
🇺🇸
Nashville, Tennessee, United States
City of Hope National Medical Center
🇺🇸
Duarte, California, United States
Washington University at St Louis
🇺🇸
Saint Louis, Missouri, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Princess Margaret Hospital
🇨🇦
Toronto, Ontario, Canada
Hospital for Sick Children
🇨🇦
Toronto, Ontario, Canada
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States