Phase 2
Completed N=35
3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia
Source: ClinicalTrials.gov NCT00381550 ↗Enrolled (actual)
35
Serious AEs
51.4%
Results posted
May 2014
Primary outcomePrimary: Response Rate Including Complete Response, Partial Response, and Hematological Improvement Assessed by Blood Cell Counts, Number of Blasts in Bone Marrow, and Clinical Evaluation — 18 participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Response Rate Including Complete Response, Partial Response, and Hematological Improvement Assessed by Blood Cell Counts, Number of Blasts in Bone Marrow, and Clinical Evaluation |
18 | — |
| PRIMARY Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0 |
35 | — |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT00381550). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.