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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Clofarabine with Busulfan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clofarabine with Busulfan<br>Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days | Drug: Clofarabine with Busulfan<br>* Clofarabine 40 mg/m2 IV QD × 5 days Busulfan (Busulfex™) 3.2 mg/kg IV QD × 2 days<br>* Other names: Busulfan: Busulfex™;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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conditioning, preparative, clofarabine; transplant, Busulfan, leukemia, myelodysplastic syndrome