Clinical Trials /

Decitabine With Ruxolitinib or Fedratinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms

NCT04282187

Description:

This phase II trial studies how well decitabine with ruxolitinib or fedratinib works before hematopoietic stem cell transplant in treating patients with accelerated/blast phase myeloproliferative neoplasms (tumors). Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ruxolitinib and fedratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy before a donor hematopoietic stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Decitabine, with ruxolitinib or fedratinib, may work better than multi-agent chemotherapy or no pre-transplant therapy, in treating patients with accelerated/blast phase myeloproliferative neoplasms.

Related Conditions:
  • Myeloproliferative Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Decitabine With Ruxolitinib or Fedratinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms
  • Official Title: A Phase 2 Trial Investigating Decitabine in Combination With a JAK-Inhibitor as a Bridge to Allogeneic Hematopoietic Stem Cell Transplant in Patients With Accelerated/Blast Phase Myeloproliferative Neoplasms

Clinical Trial IDs

  • ORG STUDY ID: RG1006644
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: NCI-2020-00749
  • NCT ID: NCT04282187

Conditions

  • Acute Myeloid Leukemia
  • Essential Thrombocythemia
  • Myelodysplastic Syndrome
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Myeloproliferative Neoplasm
  • Myeloproliferative Neoplasm, Unclassifiable
  • Polycythemia Vera
  • Primary Myelofibrosis
  • Secondary Myelofibrosis

Interventions

DrugSynonymsArms
Decitabine127716, 2''-Deoxy-5-azacytidine, 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, DezocitidineTreatment (decitabine, ruxolitinib, fedratinib)
Ruxolitinib941678-49-5, INCB-18424, Jakafi, Oral JAK Inhibitor INCB18424Treatment (decitabine, ruxolitinib, fedratinib)
Fedratinib936091-26-8, SAR302503, TG101348Treatment (decitabine, ruxolitinib, fedratinib)

Purpose

This phase II trial studies how well decitabine with ruxolitinib or fedratinib works before hematopoietic stem cell transplant in treating patients with accelerated/blast phase myeloproliferative neoplasms (tumors). Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ruxolitinib and fedratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving chemotherapy before a donor hematopoietic stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells. Decitabine, with ruxolitinib or fedratinib, may work better than multi-agent chemotherapy or no pre-transplant therapy, in treating patients with accelerated/blast phase myeloproliferative neoplasms.

Detailed Description

      OUTLINE:

      Patients receive decitabine intravenously (IV) once daily (QD) over 1 hour on days 1-10, and
      either ruxolitinib orally (PO) twice daily (BID) or fedratinib daily on days 1-28. Treatment
      repeats every 28 days for up to 6 cycles in the absence of disease progression or
      unacceptable toxicity.

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

Trial Arms

NameTypeDescriptionInterventions
Treatment (decitabine, ruxolitinib, fedratinib)ExperimentalPatients receive decitabine IV QD over 1 hour on days 1-10, and either ruxolitinib PO BID or fedratinib daily on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
  • Decitabine
  • Ruxolitinib
  • Fedratinib

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically confirmed diagnosis of MPN as defined by the 2016 World Health
             Organization criteria, consisting of polycythemia vera, essential thrombocythemia,
             primary myelofibrosis, secondary myelofibrosis, MPN-unclassifiable, or myelodysplastic
             syndrome (MDS)/MPN overlap that has progressed to either MDS or acute myeloid leukemia
             (AML) with >= 5% myeloblasts in either bone marrow or peripheral blood

          -  Outside diagnostic material is acceptable as long as peripheral blood and/or bone
             marrow slides are reviewed at the study institution by pathology. Flow cytometric
             analysis of peripheral blood and/or bone marrow should be performed according to
             institutional practice guidelines

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Karnofsky >= 60%

          -  Serum creatinine clearance >= 50 ml/min (assessed within 14 days of study day 1)

          -  Total bilirubin =< 3 unless due to Gilbert's disease or hemolysis (assessed within 14
             days of study day 1)

          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x upper limit of
             normal (ULN) unless thought to be due to MPN disease process (assessed within 14 days
             of study day 1)

          -  For patient receiving fedratinib, thiamine level should be above the laboratory lower
             limit of normal (>= 70 nmol/L in the University of Washington [UW]/Seattle Cancer Care
             Alliance [SCCA] lab). If it is low, it may be repleted but should be rechecked and
             demonstrated to normalize prior to initiation of therapy

          -  Patient is considered a potential transplant candidate. The attending/treating
             physician will determine transplant candidacy at the time of consent

          -  Capable of providing valid informed consent

        Exclusion Criteria:

          -  Previous treatment with chemotherapy (e.g. hypomethylating agents or cytarabine-based
             regimens) for MPN progressed to MDS or AML. Prior temporary measures to control blood
             counts, such as hydroxyurea or interferon, are allowed. Prior treatment with JAK
             inhibitor therapy is allowed

          -  Active systemic fungal, bacterial, viral, or other infection, unless disease is under
             treatment with anti-microbials and/or controlled or stable (e.g. if specific,
             effective therapy is not available/feasible or desired [e.g. chronic viral hepatitis,
             human immunodeficiency virus (HIV)])

          -  Known hypersensitivity to any study drug

          -  Females who are pregnant or breastfeeding

          -  Treatment with any other anti-MDS/leukemia investigational agent within 2 weeks of
             start of study drugs

          -  For patients planning to receive fedratinib: concurrent use of strong and moderate
             CYP3A4 inducers or dual CYP3A4 and CYP2C19 inhibitors that cannot be discontinued

          -  For patients planned to receive ruxolitinib AND platelets < 50,000/mm^2: concurrent
             use of a strong CYP3A4 inhibitor that cannot be discontinued
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients enrolled who receive hematopoietic stem cell transplantation (HCT)
Time Frame:Up to 5 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Time from diagnosis of myeloproliferative neoplasm (MPN)-accelerated phase (AP)/blast phase (BP) to day 0 of HCT
Time Frame:Up to day 0 of HCT
Safety Issue:
Description:Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Measure:Remission rate
Time Frame:At day 100
Safety Issue:
Description:Assessed via the Mascarenhas criteria. Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Measure:Overall survival
Time Frame:From day 0 of HCT, assessed until 12 months post HCT
Safety Issue:
Description:Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Measure:Relapse-free survival
Time Frame:From day 0 of HCT, assessed until 12 months post HCT
Safety Issue:
Description:Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Measure:Mutational profiling
Time Frame:Up to 5 years
Safety Issue:
Description:Mutational data will be descriptive. The study team will record mutations found on the next generation of sequencing assays and will watch how these profiles change over time
Measure:Response rates regardless of transplant status
Time Frame:From day 1 of study treatment, assessed up to 5 years
Safety Issue:
Description:Assessed via Mascarenhas criteria. Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Measure:Overall survival regardless of transplant status
Time Frame:From day 1 of study treatment, assessed up to 5 years
Safety Issue:
Description:Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Measure:Relapse-free survival regardless of transplant status
Time Frame:From day 1 of study treatment, assessed up to 5 years
Safety Issue:
Description:Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Washington

Trial Keywords

  • Myeloid and Monocytic Leukemia
  • Other Hematopoietic

Last Updated

February 21, 2020