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Study of Stem Cell Transplant for Leukemia and Myelodysplastic Syndromes Using Clofarabine and Busulfan Regimen

This study has been completed.
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Baylor Research Institute
ClinicalTrials.gov Identifier:
NCT00852163
First received: February 25, 2009
Last updated: April 1, 2013
Last verified: April 2013
  Purpose

The purpose of this study is to determine whether Clofarabine in combination with Busulfan is effective as a preparative transplant regimen for the treatment of leukemia and myelodysplastic syndromes


Condition Intervention Phase
Leukemia
Myelodysplastic Syndrome
Drug: Clofarabine with Busulfan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Clofarabine With Parenteral Busulfan (Busulfex®) Followed by Allogeneic Related or Unrelated Donor Transplantation for the Treatment of Hematologic Malignancies and Diseases

Resource links provided by NLM:


Further study details as provided by Baylor Research Institute:

Primary Outcome Measures:
  • Disease free survival at one and two year [ Time Frame: At 1 year and 2 Year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of hematopoietic engraftment [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Incidence and severity of acute toxicities [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic profiles of high dose busulfan and standard dose clofarabine [ Time Frame: Lesss than 8 days ] [ Designated as safety issue: No ]
  • Acute GVHD [ Time Frame: 100 Days ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: March 2007
Study Completion Date: December 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clofarabine with Busulfan
Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days
Drug: Clofarabine with Busulfan
Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days
Other Names:
  • Clofarabine:CLOLAR, clofarabine; CAFdA; Cl-F-ara-A;
  • Busulfan: Busulfex™

Detailed Description:

The success of allogeneic hematopoietic transplantation in the treatment of myeloid malignancies is determined by two main factors: the limiting of regimen-related toxicity and the prevention of recurrent leukemia. Over the past 10 years, considerable clinical research has been devoted to the reduction of regimen-related toxicity through the use of reduced-intensity (nonmyeloablative) transplants. However, leukemic relapse has remained a difficult obstacle. Thus, the need for highly effective, yet non-toxic regimens persists, particularly for elderly patients for whom very little overall progress has been made. Clofarabine is a chemotherapeutic agent with novel myelotoxic properties and proven low toxicity in older patients. These qualities suggest clofarabine may be a useful component of conditioning regimens for stem cell transplantation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Disease Criteria:

  • Acute myelogenous leukemia (AML)
  • Acute lymphocytic leukemia (ALL)
  • Myelodysplastic syndromes (MDS) Refractory anemia (RA) with adverse cytogenetics (SWOG criteria) or beyond (RAEB, RAEB-T, AML)
  • Other Myeloproliferative Disorders Myelofibrosis, Agnogenic Myeloid Metaplasia, Chronic Myelomonocytic Leukemia (CMML)
  • Chronic lymphocytic leukemia (CLL) High risk or advanced disease

Other Inclusion Criteria:

  • 18 years of age or older
  • Related or unrelated donor with HLA criteria as follows:

    • Related donors: a serologic equivalent HLA Class I (A, B, and C) and Class II DRB1 or DQB1 matched donor OR a donor who is a single 1 antigen mismatched for A, B, C, DRB1, or DQB1 loci
    • Unrelated donors: sequence-based typing fully matched A, B, C, DRB1, and DQB1 allele-matched donor OR a donor who is no greater than 1 antigen mismatched for A, B, C, DRB1, or DQB1 loci
  • Able to provide valid informed consent.
  • Female patients must have a negative serum pregnancy test within 2 weeks prior to enrollment.
  • Male and female patients must use an effective contraceptive method during the study and for up to 12 months after study treatment.

Exclusion Criteria:

Organ Function Criteria:

  • Cardiac: symptomatic coronary artery disease or ejection fraction <45% or uncontrolled cardiac failure
  • Pulmonary: FEV1 or DLCO (corrected) <50% of predicted values and/or receiving continuous supplementary oxygen
  • Hepatic: Bilirubin ≥ 1.2 mg/dL or AST/ALT ≥ 3x upper limit of normal (ULN) unless the liver is involved with malignant disease
  • Renal: creatinine clearance < 60 mL/min (24-hour urine collection) or <50 mL/min (Glofil test)
  • Karnofsky score <60%
  • Active CNS disease
  • Prior hematopoietic transplantation (autologous or allogeneic) <6 months prior to study entry
  • Use of investigational agents less than or equal to 30 days before study entry.
  • Life threatening, or clinically significant infection
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
  • Female patients who are pregnant or breast feeding
  • HIV-positive
  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: NCT00852163

Locations
United States, Texas
Baylor University Medical Center
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Baylor Research Institute
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Edward Agura, MD Baylor Health Care System
  More Information

No publications provided

Responsible Party: Baylor Research Institute
ClinicalTrials.gov Identifier: NCT00852163     History of Changes
Other Study ID Numbers: 006-150
Study First Received: February 25, 2009
Last Updated: April 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Baylor Research Institute:
conditioning, preparative
clofarabine; transplant
Busulfan
leukemia
myelodysplastic syndrome

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Busulfan
Clofarabine
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014