Busulfan, Fludarabine, Clofarabine With Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00469014
First received: May 3, 2007
Last updated: April 1, 2013
Last verified: April 2013
  Purpose

The goal of this clinical research study is to find the best dose of clofarabine and fludarabine that can be given with busulfan followed by an allogeneic blood stem cell transplant. Researchers will study whether this combination can help to control the disease, and look at the safety of this combination. Researchers also want to find out if combining busulfan with clofarabine alone or combining busulfan with both fludarabine and clofarabine will improve the treatment, compared with the previous standard method using busulfan and fludarabine alone.


Condition Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Chronic Myeloid Leukemia
Drug: Clofarabine
Drug: Busulfan
Drug: Fludarabine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Busulfan-Fludarabine-Clofarabine With Allogeneic Stem Cell Transplantation for Advanced Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Advanced, Gleevec Refractory Chronic Myeloid Leukemia. A Randomized Phase II Study.

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Optimal Dose Level [ Time Frame: Four combinations of daily doses to be studied in 4 day schedule ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Treatment Related Mortality [ Time Frame: First 30 Days ] [ Designated as safety issue: No ]

Enrollment: 72
Study Start Date: September 2006
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1: Busulfan + Fludarabine (30 mg/m^2) + Clofarabine
Busulfan 30 mg/m^2 intavenous (IV) Daily + Fludarabine 30 mg/m^2 IV Daily; + Clofarabine 10 mg/m^2 IV Daily
Drug: Clofarabine
Arm 1 = 10 mg/m^2 intavenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily
Other Names:
  • Clofarex
  • Clolar
Drug: Busulfan
Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily
Other Names:
  • Busulfex
  • Myleran
Drug: Fludarabine
Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily
Other Names:
  • Fludarabine Phosphate
  • Fludara
Experimental: Arm 2: Busulfan + Fludarabine (20 mg/m^2) + Clofarabine
Busulfan 20 mg/m^2 IV + Fludarabine 20 mg/m^2 IV Daily + Clofarabine 20 mg/m^2 IV Daily
Drug: Clofarabine
Arm 1 = 10 mg/m^2 intavenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily
Other Names:
  • Clofarex
  • Clolar
Drug: Busulfan
Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily
Other Names:
  • Busulfex
  • Myleran
Drug: Fludarabine
Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily
Other Names:
  • Fludarabine Phosphate
  • Fludara
Experimental: Arm 3: Busulfan + Fludarabine (10 mg/m^2) + Clofarabine
Busulfan 10 mg/m^2 IV Daily + Fludarabine 10 mg/m^2 IV Daily + Clofarabine 30 mg/m^2 IV Daily
Drug: Clofarabine
Arm 1 = 10 mg/m^2 intavenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily
Other Names:
  • Clofarex
  • Clolar
Drug: Busulfan
Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily
Other Names:
  • Busulfex
  • Myleran
Drug: Fludarabine
Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily
Other Names:
  • Fludarabine Phosphate
  • Fludara
Experimental: Arm 4: Busulfan + Clofarabine
Busulfan 40 mg/m^2 IV Daily + Clofarabine 40 mg/m^2 IV Daily
Drug: Clofarabine
Arm 1 = 10 mg/m^2 intavenous (IV) Daily; Arm 2 = 20 mg/m^2 IV Daily; Arm 3 = 30 mg/m^2 IV Daily; Arm 4 = 40 mg/m^2 IV Daily
Other Names:
  • Clofarex
  • Clolar
Drug: Busulfan
Arm 1: 30 mg/m^2 IV Daily; Arm 2: 20 mg/m^2 IV Daily; Arm 3: 10 mg/m^2 IV Daily; Arm 4: 40 mg/m^2 IV Daily
Other Names:
  • Busulfex
  • Myleran

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis or 1) Acute myeloid leukemia past first remission, in first or subsequent relapse, or induction failures, 2) Myelodysplastic syndromes with intermediate or high risk International Prognostic Scoring System score (IPSS scores) (16), and having failed previous chemotherapy, or 3) Chronic Myeloid Leukemia, Philadelphia-chromosome positive and having failed / being resistant to therapy based on Gleevec or other tyrosine kinase inhibitors.
  2. Patient has not been administered intensive systemic chemotherapeutic drugs within 21 days prior to trial enrollment (bone marrow transplant (BMT) Day -9). Gleevec, alternative tyrosine kinase inhibitors, other nonmyelosuppressive agents, low dose cytarabine, hydroxyurea is permitted if indicated to control the leukemia. All tyrosine inhibitor- or other non-myelosuppressive agents have to be terminated at least one week prior to admission for this treatment.
  3. No uncontrolled infection. Protocol principal investigator (PI) will be final arbiter if there is uncertainty regarding whether a previous infection is resolved on appropriate antibiotics therapy.
  4. age </= 60
  5. A related or unrelated donor who is HLA-matched or mismatched in 1 HLA, A, B, C, DR or DQ locus is acceptable (i.e. at least a 9/10 matched related or unrelated donor, matched with molecular high-resolution technique per current standard for the BMT program).
  6. ZUBROD performance status <2
  7. Life expectancy is not severely limited by concomitant illness.
  8. Left ventricular ejection fraction >/=45% No uncontrolled arrhythmias or symptomatic cardiac disease.
  9. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capacity (DLCO) >/= 50% of expected corrected for hemoglobin. In patients </= 7 years pulmonary function will be assessed per pediatric BMT routine
  10. Serum creatinine </= 1.5 mg%.
  11. Serum glutamic pyruvic transaminase (SGPT) </= 200 IU/ml, serum bilirubin and alkaline phosphatase within accepted laboratory standard normal limits or considered not clinically significant. No evidence of chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and perform liver biopsy pror to determining study eligibility.
  12. Female patient is not pregnant (negative human chorionic gonadotropin (hCG) pregnancy test in all women of child-bearing-potential in accordance with departmental routine).
  13. Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

Exclusion Criteria:

  1. Effusion or ascites estimated to be >1L prior to drainage.
  2. HIV-positive.
  3. Hepatitis C or HBsAg positive
  4. Prior stem cell transplant after a myeloablative conditioning program (such as busulfan-based using a total dose of >/= 12 mg/kg given by mouth or >/= 10 mg/kg IV, or a total-body irradiation-based program.
  5. Active or prior Central Nervous System (CNS) leukemia
  6. Biphenotypic acute leukemia.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00469014

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Richard E. Champlin, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00469014     History of Changes
Other Study ID Numbers: 2006-0200
Study First Received: May 3, 2007
Last Updated: April 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Acute Myeloid Leukemia
AML
Myelodysplastic Syndrome
MDS
Chronic Myeloid Leukemia
CML
Busulfan
Busulfex
Myleran
Fludarabine
Fludara
Fludarabine Phosphate
Clofarabine
Clofarex
Clolar
Allogeneic stem cell transplantation
ASCT
Stem Cell
Gleevec
Imatinib Mesylate

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Busulfan
Clofarabine
Fludarabine
Fludarabine phosphate
Vidarabine
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 21, 2014