This phase I/II trial studied the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS) that have relapsed or not responded to treatment.
PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) of oral clofarabine when given with LDAC (cytarabine) in patients age \>= 60 with previously treated AML or high risk MDS. SECONDARY OBJECTIVES: I. To determine the response rate, disease-free survival (DFS), and overall survival (OS) after therapy with oral clofarabine and LDAC for previously treated AML or high-risk MDS. OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by a phase II study. Patients receive clofarabine orally (PO) once daily (QD) on days 1-5 and low-dose cytarabine subcutaneously (SC) twice daily (BID) on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then annually for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Given PO
Given SC
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Number of Patients With Dose Limiting Toxicity
Dose limiting toxicity (DLT) consists of grade 3-4 non-hematologic toxicity at least possibly related to study drug. Exceptions include neutropenic fever; drug-related fever; alopecia; anorexia; inadequately treated nausea, vomiting and/or diarrhea; and grade 3/4 increase in ALT, AST, or bilirubin recovering to \< grade 2 by 7 days. Prolonged grade 2 myelosuppression lasting longer than 49 days in patients who don't proceed to additional cytotoxic therapy is considered a DLT. The MTD or recommended phase II dose is the highest dose level at which no more than 1 patient out of 6 experiences DLT.
Time frame: Outcomes by day 30
Maximum Tolerated Dose
We identified 20 mg/d for 5 d as the maximum tolerated dose (MTD) of oral clofarabine.
Time frame: up to 5 years
Treatment Response
CR = no evidence of leukemia with complete blood count recovery (ANC \>1,000 and PLTS \>100k) CRi = no evidence of leukemia but with incomplete blood count recovery
Time frame: Up to 5 years
Disease Free Survival
Median disease-free survival
Time frame: Up to 5 years
Overall Survival
Median overall survival
Time frame: Up to 5 years
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