We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00381550
Recruitment Status : Completed
First Posted : September 28, 2006
Results First Posted : May 21, 2014
Last Update Posted : January 6, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
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 Drug: fludarabine phosphate Drug: triapine Procedure: laboratory biomarker analysis Phase 2

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.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Disorders (MPDs) Including Chronic Myelomonocytic Leukemia (CMML) and Chronic Myelogenous Leukemia in Accelerated Phase (CML-AP) or Blast Crisis (CML-BC)
Study Start Date : August 2006
Actual Primary Completion Date : March 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: 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.
 Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara

Drug: triapine
Given IV
Other Names:
  • 3-AP
  • OCX-191

Procedure: laboratory biomarker analysis
Correlative study


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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.).

  2. Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0 [ Time Frame: Up to 4 years ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00381550


Locations
Layout table for location information
United States, Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Judith Karp Johns Hopkins University/Sidney Kimmel Cancer Center
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications of Results:

Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00381550    
Other Study ID Numbers: NCI-2009-00209
NCI-2009-00209 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
J0638 ( Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center )
7704 ( Other Identifier: CTEP )
P30CA006973 ( U.S. NIH Grant/Contract )
U01CA070095 ( U.S. NIH Grant/Contract )
First Posted: September 28, 2006    Key Record Dates
Results First Posted: May 21, 2014
Last Update Posted: January 6, 2015
Last Verified: June 2014
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Polycythemia Vera
Blast Crisis
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
 Hypereosinophilic Syndrome
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Chronic Disease
Disease Attributes
Pathologic Processes
Myelodysplastic-Myeloproliferative Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Blood Platelet Disorders
Blood Coagulation Disorders