Clinical trial · Interventional
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)
NCT00381550CI-TRIAL-00016522completedPhase 2Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (10)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Accelerated Phase Chronic Myelogenous Leukemia | Accelerated Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive | ALIAS | 0.90 |
| Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative | Atypical Chronic Myeloid Leukemia | ALIAS | 0.90 |
| Blastic Phase Chronic Myelogenous Leukemia | Blast Phase Chronic Myeloid Leukemia, BCR-ABL1 Positive | ALIAS | 0.90 |
| Chronic Eosinophilic Leukemia | Chronic Eosinophilic Leukemia, Not Otherwise Specified | ONTOLOGY_EXACT | 0.98 |
| Chronic Myelomonocytic Leukemia | Chronic Myelomonocytic Leukemia | ONTOLOGY_EXACT | 0.98 |
| Essential Thrombocythemia | Essential Thrombocythemia | ONTOLOGY_EXACT |
Interventions
Interventions (3)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| fludarabine phosphate | Drug | Fludarabine | ALIAS |
| laboratory biomarker analysis | Procedure | — | UNRESOLVED |
| triapine | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Arm I
- description
- 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.
- interventionNames
- Drug: fludarabine phosphate
- Drug: triapine
- Procedure: laboratory biomarker analysis
Primary outcomes (2)
- measure
- Response Rate Including Complete Response, Partial Response, and Hematological Improvement Assessed by Blood Cell Counts, Number of Blasts in Bone Marrow, and Clinical Evaluation
- timeFrame
- Up to 4 years
- description
- 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.).
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (1)
- RESULTZeidner 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