Clinical trial NCT01457885: Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloblastic Leukemia
Keywords: AML
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
name: Otsuka Pharmaceutical Development & Commercialization, Inc.
First posted: 2011-10-24
Enrollment: 75
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Cumulative Incidence of Non Relapse Mortality (NRM)
timeFrame: 1 year
Secondary outcomes:
measure: The Percentage of Patients Alive at 1 Year
timeFrame: 1 year
measure: Incidence of Relapse
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama, Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University at St Louis
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbuilt University
state: Tennessee
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University of Alabama at Birmingham
name: Shin Mineishi, MD
role: STUDY_CHAIR
affiliation: University of Michigan, Department of Internal Medicine
name: John M Magenau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: City of Hope National Medical Center
name: Stephen J Forman, MD
role: STUDY_CHAIR
References: