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

Acute Myeloblastic Leukemia Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01457885
• Other study ID #: UMCC 2011.038
• Status: Active, not recruiting
• Phase: Phase 2
• First received: October 19, 2011
• Last updated: October 14, 2014
• Start date: November 2011
• Est. completion date: March 2017

Study information

• Verified date: October 2014
• Source: University of Michigan Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 75
• Est. completion date: March 2017
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 65 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloblastic Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	University of Michigan Cancer Center	Ann Arbor	Michigan
United States	University of Alabama, Birmingham	Birmingham	Alabama
United States	City of Hope National Medical Center	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbuilt University	Nashville	Tennessee
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Washington	Seattle	Washington
United States	Washington University at St Louis	St Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
University of Michigan Cancer Center	Genzyme, a Sanofi Company, Otsuka Pharmaceutical Development & Commercialization, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival following transplant using a CloBu4 conditioning regimen for patients with non-remission AML		1 year	Yes
Secondary	Overall survival following transplant using a CloBu4 conditioning regimen for patients with non-remission AML		1 year	Yes
Secondary	Relapse Rate		2 years	Yes