Clinical Trial: 3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase II Trial of Triapine (NSC #663249, 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbone) Plus Fludarabine (NSC #312887, Fludarabine Monophosphate) in Adults With Aggressive Myeloproliferative Disord

Brief Summary: This phase II trial is studying how well giving 3-AP together with fludarabine works in treating patients with myeloproliferative disorders (MPD), chronic myelomonocytic leukemia (CMML), or accelerated phase or blastic phase chronic myelogenous leukemia. Drugs used in chemotherapy, such as 3-AP and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 3-AP may help fludarabine work better by making cancer cells more sensitive to the drug. 3-AP and fludarabine may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving 3-AP together with fludarabine may kill more cancer cells.

Detailed Summary:

OBJECTIVES:

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.

Current Primary Outcome:

• Response Rate Including Complete Response, Partial Response, and Hematological Improvement Assessed by Blood Cell Counts, Number of Blasts in Bone Marrow, and Clinical Evaluation [ Time Frame: Up to 4 years ]
  Bone marrow aspiration and biopsies were performed prior to treatment, during week 3 of the first cycle, at the time of hematologic recovery from all cycles of therapy (defined as neutrophil count >500/mm3 and platelets >20,000/mm3 independently of transfusion), or at any time that leukemia regrowth was suspected. The overall response rate was defined as complete remission, partial remission, or hematologic improvement, lasting for ≥30 days. Given the different subsets of diseases, standardized response criteria were used for CMML (the Myelodysplastic Syndrome International Working Group criteria),33 CMML transforming to acute myeloid leukemia (standard AML response criteria) , accelerated MPN (Giles et al.), and transformation of MPN to secondary AML (Mascarenhas et al.).
• Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0 [ Time Frame: Up to 4 years ]

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: September 26, 2006
Date Started: August 2006
Date Completion:
Last Updated: December 16, 2014
Last Verified: June 2014