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

Phase 2

Completed

• Conditions: Leukemia; Myelodysplastic Syndrome
• Interventions: Drug: Clofarabine with Busulfan

• Registration Number: NCT00852163
• Lead Sponsor: Baylor Research Institute

Brief Summary

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

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 Timeline

• Study Start: 2007-03
• Study First Submitted: 2009-02-25
• Study First Submitted QC: 2009-02-25
• Study First Posted: 2009-02-26
• Primary Completion: 2011-08
• Study Completion: 2011-12
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-01
• Last Update Posted: 2013-04-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Clofarabine with Busulfan	Clofarabine with Busulfan	Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days

Primary Outcome Measures

Name	Time	Method
Disease free survival at one and two year	At 1 year and 2 Year

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Baylor University Medical Center; 🇺🇸 Dallas, Texas, United States