study of stem cell transplant for leukemia and myelodysplastic syndromes using clofarabine and busulfan regimen

Conditions: Leukemia; Myelodysplastic Syndrome

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

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 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

Keywords: conditioning, preparative clofarabine; transplant busulfan leukemia myelodysplastic syndrome