- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00381550
3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia
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 Overview
Status
Conditions
- Primary Myelofibrosis
- Polycythemia Vera
- Essential Thrombocythemia
- Chronic Myelomonocytic Leukemia
- Accelerated Phase Chronic Myelogenous Leukemia
- Relapsing Chronic Myelogenous Leukemia
- Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
- Philadelphia Chromosome Negative Chronic Myelogenous Leukemia
- Blastic Phase Chronic Myelogenous Leukemia
- Chronic Eosinophilic Leukemia
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
Maryland
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Baltimore, Maryland, United States, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
Given IV
Other Names:
Given IV
Other Names:
Correlative study
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.).
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Up to 4 years
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Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0
Time Frame: Up to 4 years
|
Up to 4 years
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Bone Marrow Diseases
- Hematologic Diseases
- Hemorrhagic Disorders
- Neoplastic Processes
- Blood Coagulation Disorders
- Blood Platelet Disorders
- Myelodysplastic-Myeloproliferative Diseases
- Leukocyte Disorders
- Eosinophilia
- Cell Transformation, Neoplastic
- Carcinogenesis
- Chromosome Aberrations
- Translocation, Genetic
- Bone Marrow Neoplasms
- Hematologic Neoplasms
- Primary Myelofibrosis
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelomonocytic, Acute
- Leukemia, Myelomonocytic, Chronic
- Leukemia, Myelomonocytic, Juvenile
- Thrombocytosis
- Thrombocythemia, Essential
- Hypereosinophilic Syndrome
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Blast Crisis
- Leukemia, Myeloid, Accelerated Phase
- Myeloproliferative Disorders
- Philadelphia Chromosome
- Polycythemia Vera
- Polycythemia
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Fludarabine
- Fludarabine phosphate
Other Study ID Numbers
- NCI-2009-00209 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA006973 (U.S. NIH Grant/Contract)
- U01CA070095 (U.S. NIH Grant/Contract)
- 7704 (Other Identifier: CTEP)
- J0638 (Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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