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

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ClinicalTrials.gov Identifier: NCT04282187
Recruitment Status : Recruiting
First Posted : February 24, 2020
Last Update Posted : August 27, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

Tracking Information
First Submitted Date  ICMJE February 19, 2020
First Posted Date  ICMJE February 24, 2020
Last Update Posted Date August 27, 2020
Actual Study Start Date  ICMJE March 24, 2020
Estimated Primary Completion Date November 11, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 21, 2020)
Proportion of patients enrolled who receive hematopoietic stem cell transplantation (HCT) [ Time Frame: Up to 5 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 21, 2020)
  • 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 ]
    Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
  • Remission rate [ Time Frame: At day 100 ]
    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.
  • Overall survival [ Time Frame: From day 0 of HCT, assessed until 12 months post HCT ]
    Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
  • Relapse-free survival [ Time Frame: From day 0 of HCT, assessed until 12 months post HCT ]
    Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
  • Mutational profiling [ Time Frame: Up to 5 years ]
    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
  • Response rates regardless of transplant status [ Time Frame: From day 1 of study treatment, assessed up to 5 years ]
    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.
  • Overall survival regardless of transplant status [ Time Frame: From day 1 of study treatment, assessed up to 5 years ]
    Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
  • Relapse-free survival regardless of transplant status [ Time Frame: From day 1 of study treatment, assessed up to 5 years ]
    Estimated as a simple proportion and informally compared to rates seen historically among patients treated with multi-agent chemotherapy or no pre-HCT therapy.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Decitabine With Ruxolitinib or Fedratinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms
Official Title  ICMJE 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
Brief Summary 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 PO 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Essential Thrombocythemia
  • Myelodysplastic Syndrome
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Myeloproliferative Neoplasm
  • Myeloproliferative Neoplasm, Unclassifiable
  • Polycythemia Vera
  • Primary Myelofibrosis
  • Secondary Myelofibrosis
Intervention  ICMJE
  • Drug: Decitabine
    Given IV
    Other Names:
    • 127716
    • 2''-Deoxy-5-azacytidine
    • 5-Aza-2''-deoxycytidine
    • Dacogen
    • Decitabine for Injection
    • Deoxyazacytidine
    • Dezocitidine
  • Drug: Ruxolitinib
    Given PO
    Other Names:
    • 941678-49-5
    • INCB-18424
    • Jakafi
    • Oral JAK Inhibitor INCB18424
  • Drug: Fedratinib
    Given PO
    Other Names:
    • 936091-26-8
    • SAR302503
    • TG101348
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE Experimental: Treatment (decitabine, ruxolitinib, fedratinib)
Patients receive decitabine IV QD over 1 hour on days 1-10, and either ruxolitinib PO BID or fedratinib PO daily on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Decitabine
  • Drug: Ruxolitinib
  • Drug: Fedratinib
  • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 21, 2020)
25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 11, 2024
Estimated Primary Completion Date November 11, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Pathologically confirmed diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with >= 5% myeloblasts in either bone marrow or peripheral blood felt to be transformed out of an MPN as defined by the 2016 World Health Organization criteria, consisting of polycythemia vera, essential thrombocythemia, primary myelofibrosis, secondary myelofibrosis, MPN-unclassifiable, or MDS/MPN overlap
  • 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 calculated by the Cockcroft-Gault Equation (assessed within 14 days of study day 1)
  • Total bilirubin =< 3 unless due to Gilbert's disease or hemolysis (total bilirubin > 3 is allowable if thought due to Gilbert's disease, hemolysis, or MPN disease) (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 (AST/ALT > 3 is allowable if thought due to MPN disease) (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
  • The use of hydroxyurea prior to study registration is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood count (WBC) > 100,000/uL, or with concern for other complications of high tumor burden or leukostasis (e.g. hypoxia, disseminated intravascular coagulation) can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m^2 /dose) anytime prior to enrollment
  • 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 is allowed. Prior treatment with hydroxyurea, interferons or 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Kelsey-Leigh Garcia 206.606.7537 klgarcia@seattlecca.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04282187
Other Study ID Numbers  ICMJE RG1006644
P30CA015704 ( U.S. NIH Grant/Contract )
NCI-2020-00749 ( Registry Identifier: NCI / CTRP )
10419 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Washington
Study Sponsor  ICMJE University of Washington
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Anna Halpern Fred Hutch/University of Washington Cancer Consortium
PRS Account University of Washington
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP