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Accelerated Phase Chronic Myelogenous LeukemiaPhase 2NCT00381550

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

A Phase 2 study testing fludarabine phosphate, triapine and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
fludarabine phosphate, triapine and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
Aug 2006to Mar 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

Other trials in United States

About this study

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)

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.

Read the detailed description

OBJECTIVES:

  1. 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.

Being tested
fludarabine phosphate, triapine, laboratory biomarker analysis
Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Blast Crisis, Pdgfra-Associated Chronic Eosinophilic Leukemia, Leukemia, Myelomonocytic, Chronic, Thrombocythemia, Essential, Polycythemia Vera, Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

  • triapineDrug

    Also called 3-AP, OCX-191

    Given IV

  • laboratory biomarker analysisProcedure or surgery

    Correlative study

Study groups in NCT00381550
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: fludarabine phosphate; Drug: triapine; Procedure: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    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.).

    Measured: Up to 4 years

  2. Incidence of Grade 3 or 4 Drug-related Non-hematologic Toxicity as Assessed by NCI CTCAE v3.0

    Measured: Up to 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionMar 2011
  4. Study completionMar 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00381550
Sponsor's protocol ID
NCI-2009-00209
Other IDs
NCI-2009-00209, J0638, 7704, P30CA006973, U01CA070095
Status last verified
Jun 2014
First submitted
26 Sep 2006
Last updated
6 Jan 2015
Data monitoring committee
No

Publications

  • Zeidner 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.

    PubMed 24362550

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing fludarabine phosphate, triapine and laboratory biomarker analysis in people with Accelerated Phase Chronic Myelogenous Leukemia and Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Up to 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00381550, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2015.

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