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

NCT ID: NCT00381550

Last Updated: 2015-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-08-31
• Study Completion Date: 2011-03-31

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 Description

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.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Polycythemia Vera; Primary Myelofibrosis; Relapsing Chronic Myelogenous Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

fludarabine phosphate

Intervention Type: DRUG

Given IV

triapine

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: PROCEDURE

Correlative study

Interventions

fludarabine phosphate

Given IV

Intervention Type: DRUG

triapine

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative study

Intervention Type: PROCEDURE

Other Intervention Names

2-F-ara-AMP; Beneflur; Fludara; 3-AP; OCX-191

Eligibility Criteria

Inclusion Criteria

• ECOG performance status 0-2
• Negative pregnancy test
• Fertile patients must use effective contraception
• No chronic toxicity from prior chemotherapy > grade 1
• No history of severe coronary artery disease
• Creatinine normal OR creatinine clearance >= 60 mL/min
• AST and ALT =< 2.5 times normal
• Bilirubin =< 2.0 mg/dL unless due to leukemia, Gilbert's syndrome, or hemolysis
• No arrhythmias (other than atrial flutter or fibrillation) requiring medication
• No uncontrolled congestive heart failure
• No dyspnea at rest or with minimal exertion
• No severe pulmonary disease requiring supplemental oxygen
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to 3-AP (Triapine®) and/or fludarabine phosphate
• No other life-threatening illness
• No history of mental deficits and/or psychiatric illness that would preclude study compliance
• No more than 4 prior induction regimens (3 cytotoxic chemotherapy regimens)
• At least 3 weeks since prior myelosuppressive cytotoxic agents (6 weeks for mitomycin C or nitrosoureas) and recovered
• At least 1 week since prior nonmyelosuppressive treatment
• At least 48 hours since prior noncytotoxic agents for peripheral blood leukemic cell count control, including but not limited to the following:

• Hydroxyurea
• Imatinib mesylate
• Interferon
• Mercaptopurine
• Cyclophosphamide
• At least 2 weeks since prior and no concurrent radiotherapy to treat cancer
• At least 1 week since prior biologic therapy, including hematopoietic growth factors (e.g., epoetin alfa, darbepoetin alfa, filgrastim [G-CSF], sargramostim [GM-CSF], interleukin-3, or interleukin-11)
• No other concurrent chemotherapy to treat cancer
• No concurrent immunotherapy to treat cancer
• No known glucose-6-phosphate dehydrogenase [G6PD) deficiency (G6PD screening required for high-risk groups (i.e., patients of African, Asian, or Mediterranean origin/ancestry)]
• No active heart disease
• No concurrent myeloid growth factors
• No active uncontrolled infection (Infections under active treatment and controlled with antibiotics are allowed)
• No chronic hepatitis

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith Karp

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University/Sidney Kimmel Cancer Center

Locations

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Countries

United States

References

Zeidner JF, Karp JE, Blackford AL, Smith BD, Gojo I, Gore SD, Levis MJ, Carraway HE, Greer JM, Ivy SP, Pratz KW, McDevitt MA. A phase II trial of sequential ribonucleotide reductase inhibition in aggressive myeloproliferative neoplasms. Haematologica. 2014 Apr;99(4):672-8. doi: 10.3324/haematol.2013.097246. Epub 2013 Dec 20.

Reference Type: RESULT

PMID: 24362550 (View on PubMed)

Other Identifiers

NCI-2009-00209

Identifier Type: REGISTRY

Identifier Source: secondary_id

J0638

Identifier Type: OTHER

Identifier Source: secondary_id

7704

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA070095

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00209

Identifier Type: -

Identifier Source: org_study_id