A Phase 2 interventional study of fludarabine phosphate and triapine in Accelerated Phase Chronic Myelogenous Leukemia, Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative and Blastic Phase Chronic Myelogenous Leukemia, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-01-06.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
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.
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.
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Criteria:
Histopathologically confirmed diagnosis of 1 of the following:
Myeloproliferative disorders (MPDs) in aggressive phase or transformation, including the following:
Patients with aggressive phase MPD (PV, ET, or Ph- CML) must meet ≥ 1 of the following criteria:
At least 48 hours since prior noncytotoxic agents for peripheral blood leukemic cell count control, including but not limited to the following:
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
Given IV
Also known as: 2-F-ara-AMP, Beneflur, Fludara
Given IV
Also known as: 3-AP, OCX-191
Correlative study
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.).
Time frame: Up to 4 years
Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0
Time frame: Up to 4 years
Patient's presenting for treatment of a myeloproliferative disease were considered for participation.
| Milestone | Triapine and Fludarabine Phosphate |
|---|---|
| Started | 35 |
| Completed | 35 |
| Not completed | 0 |
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.).
| participants | Arm I |
|---|---|
| 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 | Arm I |
|---|---|
| Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0 | 35 |
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I | — | 18/35 (51.4%) | 35/35 (100%) |
| Event | Arm I |
|---|---|
| InfectionsInfections and infestations | 7/35 |
| Kidney injuryInvestigations | 6/35 |
| Tumor Lysis syndromeMetabolism and nutrition disorders | 3/35 |
| HyperbilirubinemiaMetabolism and nutrition disorders | 2/35 |
| Event | Arm I |
|---|---|
| Elevated bilirubinMetabolism and nutrition disorders | 14/35 |
| FeverGeneral disorders | 11/35 |
| AcidosisMetabolism and nutrition disorders | 10/35 |
| Elevated creatinineMetabolism and nutrition disorders | 8/35 |
| Allergic reactionGeneral disorders | 5/35 |
| AnaphylaxisGeneral disorders | 2/35 |
| Age, Categorical(Participants) | Arm I |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 17 |
| >=65 years | 18 |
| Age, Continuous(years) | Arm I |
|---|---|
| Mean | 65 ± 40 |
| Sex: Female, Male(Participants) | Arm I |
|---|---|
| Female | 18 |
| Male | 17 |
| Region of Enrollment(participants) | Arm I |
|---|---|
| United States | 35 |
This study is completed, as verified in Jun 2014. You cannot join it, but the record below documents what was studied.
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National Cancer Institute (NCI)