Phase II Trial of Triapine (IND #68338, NSC #663249, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbone) Plus Fludarabine (NSC #312887, Fludarabine Monophosphate) in Adults With Aggressive Myeloproliferative Disorders (MPDs) Including Chronic Myelomonocytic Leukemia (CMML) and Chronic Myelogenous Leukemia in Accelerated Phase (CML-AP) or Blast Crisis (CML-BC)
I. Determine the efficacy of 3-AP (Triapine®) followed by fludarabine phosphate in patients
with myeloproliferative disorders or chronic myelomonocytic leukemia in aggressive phase or
transformation or chronic myelogenous leukemia in accelerated phase or blast crisis.
II. Determine the toxicity of this regimen in these patients. III. Determine, preliminarily,
the effect of this regimen on circulating leukemic cell genetics in these patients.
Outline: This is an open-label study.
Patients receive 3-AP (Triapine®) IV over 4 hours followed by fludarabine phosphate IV over
30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression
or unacceptable toxicity. Patients undergo bone marrow and/or peripheral blood collection at
baseline and periodically during study treatment for molecular analysis of Janus kinase 2
(JAK2) mutations, GATA-1 mutations, and expression of the death-inducer-obliterator (Dido)
genes on chromosome 20q.
After completion of study treatment, patients are followed periodically.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate including complete response, partial response, and hematological improvement assessed by blood cell counts, number of blasts in bone marrow, and clinical evaluation
Up to 4 years
Johns Hopkins University
United States: Food and Drug Administration
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