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

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

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

Study Overview

• Status: Completed
• Conditions: Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Clofarabine with Busulfan

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival at one and two year	At 1 year and 2 Year

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of hematopoietic engraftment	100 days
Incidence and severity of acute toxicities	100 days
Pharmacokinetic profiles of high dose busulfan and standard dose clofarabine	Lesss than 8 days
Acute GVHD	100 Days

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Collaborators: Genzyme, a Sanofi Company
• Investigators: Principal Investigator: Edward Agura, MD, Baylor Health Care System

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): August 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: February 25, 2009
• First Submitted That Met QC Criteria: February 25, 2009
• First Posted (Estimate): February 26, 2009

Study Record Updates

• Last Update Posted (Estimate): April 4, 2013
• Last Update Submitted That Met QC Criteria: April 1, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: leukemia; Busulfan; myelodysplastic syndrome; conditioning, preparative; clofarabine; transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Clofarabine; Busulfan
• Other Study ID Numbers: 006-150