Clinical Trials /

Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia

NCT02257138

Description:

This phase I/II trial studies the side effects and best dose of ruxolitinib phosphate when given together with decitabine and to see how well they work in treating patients with acute myeloid leukemia that has come back or is not responding to treatment, or has developed from a type of bone marrow diseases called myeloproliferative neoplasms. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ruxolitinib phosphate together with decitabine may be an effective treatment for acute myeloid leukemia.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib Phosphate and Decitabine in Treating Patients With Relapsed or Refractory or Post Myeloproliferative Acute Myeloid Leukemia
  • Official Title: Phase I/II Study of Ruxolitinib Plus Decitabine in Patients With Post Myeloproliferative Neoplasm - Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: 2014-0344
  • SECONDARY ID: NCI-2014-02299
  • SECONDARY ID: 2014-0344
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02257138

Conditions

  • Blasts More Than 20 Percent of Bone Marrow Nucleated Cells
  • Blasts More Than 20 Percent of Peripheral Blood White Cells
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Recurrent Acute Myeloid Leukemia
  • Refractory Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Decitabine5-Aza-2'-deoxycytidine, Aza-TdC, Dacogen, Decitabine for Injection, Deoxyazacytidine, DezocitidineTreatment (ruxolitinib phosphate, decitabine)
Ruxolitinib PhosphateINCB-18424 Phosphate, JakafiTreatment (ruxolitinib phosphate, decitabine)

Purpose

This phase I/II trial studies the side effects and best dose of ruxolitinib phosphate when given together with decitabine and to see how well they work in treating patients with acute myeloid leukemia that has come back or is not responding to treatment, or has developed from a type of bone marrow diseases called myeloproliferative neoplasms. Ruxolitinib phosphate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ruxolitinib phosphate together with decitabine may be an effective treatment for acute myeloid leukemia.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the tolerability of the combination of decitabine and ruxolitinib phosphate
      (ruxolitinib [DI]) in patients with leukemia. (Phase I) II. To determine the efficacy of
      ruxolitinib in increasing and prolonging response induced by decitabine alone in patients
      with post myeloproliferative neoplasm acute myeloid leukemia (AML) (post MPN-AML)
      alternatively referred to as (myeloproliferative neoplasm - blast phase; MPN-BP). (Compared
      to historical response rate with decitabine alone) (Phase II)

      SECONDARY OBJECTIVES:

      I. To compare whether there is a difference in response rate patients with post-MPN AML with
      janus kinase 2 (JAK2) mutations and patients without JAK2 mutations.

      OUTLINE: This is a phase I, dose-escalation study of ruxolitinib phosphate followed by a
      phase II study.

      Patients receive ruxolitinib phosphate orally (PO) twice daily (BID) on days 1-28 and
      decitabine intravenously (IV) over 1-2 hours on days 1-5. Treatment repeats every 4-6 weeks
      for up to 24 courses in the absence of disease progression or unacceptable toxicity.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (ruxolitinib phosphate, decitabine)ExperimentalPatients receive ruxolitinib phosphate PO BID on days 1-28 and decitabine IV on days 1-5. Treatment repeats every 4-6 weeks for up to 24 courses in the absence of disease progression or unacceptable toxicity.
  • Decitabine
  • Ruxolitinib Phosphate

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of AML (World Health Organization [WHO] classification definition of >= to
             20% blasts)

          -  In the phase I portion of the study all patients with relapsed or refractory AML are
             eligible; for the Phase II portion of the study, patients must have AML progressing
             from prior MPN (MPN-BP) or have myelodysplastic syndrome (MDS)/MPN with more than 20%
             blasts; temporary prior measures to control blood counts, such as apheresis or Hydrea
             are allowed; patients with newly diagnosed or previously treated disease are eligible
             as long as prior therapy does not include hypomethylating agents; prior therapy for
             ruxolitinib for MPN is allowed

          -  Serum biochemical values with the following limits unless considered due to leukemia:

          -  Creatinine =< 1.5 mg/dl

          -  Total bilirubin =< 1.5 mg/dL, unless increase is due to hemolysis or congenital
             disorder

          -  Transaminases (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x upper limit of
             normal (ULN)

          -  Ability to take oral medication

          -  Ability to understand and provide signed informed consent

          -  Performance status =< 3, unless directly related to disease process as determined by
             the principal investigator

        Exclusion Criteria:

          -  Any coexisting medical condition that in the judgment of the treating physician is
             likely to interfere with study procedures or results including uncontrolled severe
             infections, as well as uncontrolled cardiac disease, or other organ dysfunction;
             patients with history of tuberculosis, human immunodeficiency virus (HIV) or hepatitis
             B and C are excluded

          -  Nursing women, women of childbearing potential with positive blood pregnancy test
             within 30 days of study start, or women of childbearing potential who are not willing
             to maintain adequate contraception (such as birth control pills, intrauterine device
             [IUD], diaphragm, abstinence, or condoms by their partner) over the entire course of
             the study

          -  Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks
             prior to study entry, excluding the placement of vascular access

          -  Active clinically serious and uncontrolled infection
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose of ruxolitinib phosphate, defined as the dose at which 0 or 1 of 6 patients experience dose-limiting toxicity (Phase I)
Time Frame:Up to 6 weeks
Safety Issue:
Description:Descriptive summaries will be provided for all patients for each safety parameter by course, grade, and relationship to treatment.

Secondary Outcome Measures

Measure:Proportion of patients without JAK2 mutations and any difference in response rate
Time Frame:Baseline
Safety Issue:
Description:The association between response and patient and disease characteristics will be examined by two-sample t-test (or Wilcoxon rank-sum test) or chi-square test.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

November 9, 2018