Clinical Trials /

Ruxolitinib Phosphate and Azacytidine in Treating Patients With Myelofibrosis or Myelodysplastic Syndrome/Myeloproliferative Neoplasm

NCT01787487

Description:

This phase II trial studies how well ruxolitinib phosphate and azacytidine work in treating patients with myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm. 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 azacytidine, 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 and azacytidine may be an effective treatment for myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm.

Related Conditions:
  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Ruxolitinib Phosphate and Azacytidine in Treating Patients With Myelofibrosis or Myelodysplastic Syndrome/Myeloproliferative Neoplasm
  • Official Title: Evaluation of Ruxolitinib and Azacytidine Combination as a Therapy for Patients With Myelofibrosis and Myelodysplastic Syndrome/ Myeloproliferative Neoplasm

Clinical Trial IDs

  • ORG STUDY ID: 2012-0737
  • SECONDARY ID: NCI-2013-00704
  • SECONDARY ID: 2012-0737
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT01787487

Conditions

  • Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis

Interventions

DrugSynonymsArms
Azacitidine5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, VidazaArm I (MF patients)
Ruxolitinib PhosphateINCB-18424 Phosphate, JakafiArm I (MF patients)

Purpose

This phase II trial studies how well ruxolitinib phosphate and azacytidine work in treating patients with myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm. 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 azacytidine, 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 and azacytidine may be an effective treatment for myelofibrosis or myelodysplastic syndrome/myeloproliferative neoplasm.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the efficacy of the combination of RUX (ruxolitinib phosphate) with AZA
      (azacytidine) in patients with myelofibrosis (MF) (primary myelofibrosis, post polycythemia
      vera myelofibrosis, or post essential thrombocythemia myelofibrosis [PMF, post- PV MF, or
      post - ET MF]) in achieving objective improvements in disease status.

      II. To determine the efficacy of the combination of RUX + AZA in patients with
      myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) including chronic
      myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (breakpoint cluster region
      [BCR]-c-abl oncogene 1, non-receptor tyrosine kinase [ABL1] negative: aCML), and
      myelodysplastic syndromes/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U), in
      achieving objective improvements in disease status.

      SECONDARY OBJECTIVES:

      I. To determine the safety of the RUX + AZA combination in patients with MF and MDS/MPN.

      TERTIARY OBJECTIVES:

      I. To explore time to response (TTR) and duration of response (DOR). II. To explore the
      effect of the combination on anemia and transfusion dependence in patients with MF and
      MDS/MPN.

      III. To explore the impact of baseline mutational profile on International Working Group
      (IWG)-Myeloproliferative Neoplasms Research and Treatment (MRT) response and overall survival
      in patients with MF and MDS/MPN.

      IV. To explore the impact of baseline anemia on overall survival in patients with MF and
      MDS/MPN.

      OUTLINE: Patients are assigned to 1 of 2 treatment arms.

      ARM I (MF): Patients with MF receive ruxolitinib phosphate orally (PO) twice daily (BID) on
      days 1-28. Beginning course 4, patients also receive azacytidine subcutaneously (SC) or
      intravenously (IV) for 5 days. Treatment repeats every 28 days for 15 courses in the absence
      of disease progression or unacceptable toxicity.

      ARM II (MDS/MPN): Patients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in
      Arm I.

      After completion of study treatment, patients are followed up for 30 days and up to 5 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm I (MF patients)ExperimentalPatients with MF receive ruxolitinib phosphate PO BID on days 1-28. Beginning course 4, patients also receive azacytidine SC or IV for 5 days. Treatment repeats every 28 days for 15 courses in the absence of disease progression or unacceptable toxicity.
  • Azacitidine
  • Ruxolitinib Phosphate
Arm II (MDS/MPN patients)ExperimentalPatients with MDS/MPN receive ruxolitinib phosphate and azacytidine as in Arm I.
  • Azacitidine
  • Ruxolitinib Phosphate

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with a diagnosis of primary myelofibrosis (PM), post polycythemia vera
             myelofibrosis (PPV MF), or post essential thrombocythemia myelofibrosis (PET MF)
             requiring therapy, including those previously treated and relapsed or refractory, or
             if newly diagnosed, with intermediate or high risk according to International Working
             Group (IWG-MRT) criteria

          -  Patients with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm,
             unclassifiable (MDS/MPN-U) that require therapy

          -  Understanding and voluntarily signing an Institutional Review Board (IRB)-approved
             informed consent form

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

          -  Direct bilirubin of =< 2 mg/dL

          -  Serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN) or 5
             x ULN if related to MF or MDS/MPN associated liver infiltration

          -  If total bilirubin is =< 2, fractionation is not required for eligibility
             determination

          -  Creatinine =< 2.5 mg/dL

          -  Platelets >= 50 x 10^9/L

          -  Absolute neutrophil count (ANC) >= 1.0 x 10^9/L

        Exclusion Criteria:

          -  For the MF and MDS/MPN-U arms (arms 1 & 2), use of any other standard drug (except
             hydroxyurea, anagrelide, growth factors, Revlimid, clofarabine, etc) or experimental
             drug or therapy within 14 days of starting study therapy

          -  Patients previously treated with RUX or AZA (only applicable for the MF and MDS/MPN
             arms)

          -  Any serious psychological condition or psychiatric illness that would prevent the
             subject from signing the informed consent document, in the investigator opinion

          -  Pregnant or lactating females

          -  Subjects of childbearing potential who are unwilling to take appropriate precautions
             (from screening through follow-up) to avoid becoming pregnant or fathering a child;
             females of non-childbearing potential are defined as women who a) are 55 years of age
             with history of amenorrhea for 1 year OR b) are surgically sterile for at least 3
             months; for females of childbearing potential, or for males, pregnancy must be avoided
             by taking appropriate precautions; these precautions and the methods of contraception
             should be communicated to the subjects and their understanding confirmed

          -  Any condition which places the subject at unacceptable risk if he/she were to
             participate in the study or confounds the ability to interpret data from the study

          -  Known positive for human immunodeficiency virus (HIV) or with known active infectious
             hepatitis, type A, B or C

          -  Patients with active malignancy of other type than required for this study, are not
             eligible with the exception of currently treated basal cell, squamous cell carcinoma
             of the skin, or carcinoma "in situ" of the cervix or breast; patients with
             malignancies with indolent behavior such as prostate cancer treated with radiation or
             surgery can be enrolled in the study as long as they have a reasonable expectation to
             have been cured with the treatment modality received
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (complete remission, partial remission, clinical improvement) in patients with myelofibrosis
Time Frame:Up to 24 weeks
Safety Issue:
Description:The method of Thall, Simon and Estey will be used for futility monitoring for this study. The objective response rate will be estimated along with the Bayesian 95% credible interval.

Secondary Outcome Measures

Measure:Incidence of adverse events defined as grade 3-4 clinically relevant non-hematologic toxicity or a serious adverse event that is felt to be drug related as assessed by the Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 30 days after completion of study treatment
Safety Issue:
Description:The method of Thall, Simon and Estey will be used for toxicity monitoring for this study.

Details

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

Last Updated

October 17, 2019