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

NCT00381550 | Completed Phase 2 Results

• 5 other identifiers: NCI-2009-00209J06387704P30CA006973U01CA070095
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Response Rate Including Complete Response, Partial Response, and Hematological Improvement Assessed by Blood Cell Counts, Number of Blasts in Bone Marrow, and Clinical Evaluation

  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.).

  Up to 4 years

• Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0

  Up to 4 years

Study Arms (1)

Arm I

EXPERIMENTAL

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.

Drug: fludarabine phosphate; Drug: triapine; Procedure: laboratory biomarker analysis

Interventions

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Arm I

triapine DRUG

Given IV

Also known as: 3-AP, OCX-191

Arm I

laboratory biomarker analysis PROCEDURE

Correlative study

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Criteria: * Not pregnant or nursing * Histopathologically confirmed diagnosis of 1 of the following: * Myeloproliferative disorders (MPDs) in aggressive phase or transformation * CML in accelerated phase or blast crisis * Chronic myelomonocytic leukemia in aggressive phase (5-19% bone marrow blasts) or transformation (\> 20% bone marrow blasts) * Myeloproliferative disorders (MPDs) in aggressive phase or transformation, including the following: * Polycythemia vera (PV) * Essential thrombocythemia (ET) * Myelofibrosis with myeloid metaplasia * Hypereosinophilic syndrome * Atypical (Philadelphia chromosome negative) chronic myelogenous leukemia (Ph- CML) * Patients with aggressive phase MPD (PV, ET, or Ph- CML) must meet ≥ 1 of the following criteria: * Marrow blasts \> 5% * Peripheral blood blasts plus progranulocytes \> 10% * New onset or increasing myelofibrosis * New onset or \> 25% increase in hepatomegaly or splenomegaly * New onset constitutional symptoms (fever, weight loss, splenic pain, bone pain) * Multilineage bone marrow failure * Ineligible for established curative regimens, including stem cell transplantation * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• 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.

  PMID: 24362550 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Blast Crisis; Pdgfra-Associated Chronic Eosinophilic Leukemia; Leukemia, Myelomonocytic, Chronic; Thrombocythemia, Essential; Polycythemia Vera; Primary Myelofibrosis

Interventions

fludarabine phosphate; 3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Condition Hierarchy (Ancestors)

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myelodysplastic-Myeloproliferative Diseases; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Michael McDevitt, MD PhD
• Organization: Sidney Kimmel Comprehensive Cancer Center

mmcdev1@jhmi.edu

410-955-9175

Study Officials

• Judith Karp

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2006
• First Posted: September 28, 2006
• Study Start: August 1, 2006
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: January 6, 2015
• Results First Posted: May 21, 2014

Record last verified: 2014-06

Locations

US (1)