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

NCT04282187 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: RG1006644NCI-2020-0074910419
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well decitabine with ruxolitinib, fedratinib, or pacritinib 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, fedratinib, and pacritinib 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, fedratinib, or pacritinib may work better than multi-agent chemotherapy or no pre-transplant therapy, in treating patients with accelerated/blast phase myeloproliferative neoplasms.

Conditions

Essential Thrombocythemia; Myelodysplastic Syndrome; Myelodysplastic/Myeloproliferative Neoplasm; Myeloproliferative Neoplasm; Myeloproliferative Neoplasm, Not Otherwise Specified; Polycythemia Vera; Primary Myelofibrosis; Secondary Myelofibrosis; Acute Myeloid Leukemia

Keywords

Myeloid and Monocytic Leukemia; Other Hematopoietic

Outcome Measures

Primary Outcomes (1)

• Proportion of patients enrolled who receive hematopoietic stem cell transplantation (HCT)

  Up to 5 years

Secondary Outcomes (8)

• Time from diagnosis of myeloproliferative neoplasm (MPN)-accelerated phase (AP)/blast phase (BP) to day 0 of HCT

  Up to day 0 of HCT

• Remission rate

  At day 100

• Overall survival

  From day 0 of HCT, assessed until 12 months post HCT

• Relapse-free survival

  From day 0 of HCT, assessed until 12 months post HCT

• Mutational profiling

  Up to 5 years

Study Arms (1)

Treatment (decitabine, ruxolitinib, fedratinib, pacritinib)

EXPERIMENTAL

Patients receive decitabine IV QD over 1 hour on days 1-10, and either ruxolitinib PO BID, fedratinib PO daily, or pacritinib PO BID on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood and bone marrow samples throughout the trial.

Drug: Decitabine; Drug: Ruxolitinib; Drug: Fedratinib; Other: Questionnaire Administration; Drug: Pacritinib; Procedure: Biospecimen Collection

Interventions

Decitabine DRUG

Given IV

Also known as: 127716, 2''-Deoxy-5-azacytidine, 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (decitabine, ruxolitinib, fedratinib, pacritinib)

Ruxolitinib DRUG

Given PO

Also known as: 941678-49-5, INCB-18424, Jakafi, Oral JAK Inhibitor INCB18424

Treatment (decitabine, ruxolitinib, fedratinib, pacritinib)

Fedratinib DRUG

Given PO

Also known as: 936091-26-8, SAR302503, TG101348

Treatment (decitabine, ruxolitinib, fedratinib, pacritinib)

Questionnaire Administration OTHER

Ancillary studies

Treatment (decitabine, ruxolitinib, fedratinib, pacritinib)

Pacritinib DRUG

Given PO

Also known as: 937272-79-2, Oral JAK2 Inhibitor SB1518, SB 1518, SB-1518, SB1518

Treatment (decitabine, ruxolitinib, fedratinib, pacritinib)

Biospecimen Collection PROCEDURE

Undergo collection of blood and bone marrow samples

Also known as: Biological Sample Collection

Treatment (decitabine, ruxolitinib, fedratinib, pacritinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years
• History of MPN as defined by the 2016 World Health Organization criteria, with now pathologically confirmed \>= 5% blasts in the bone marrow or peripheral blood. Prior MPNs could include polycythemia vera, essential thrombocythemia, primary myelofibrosis, secondary myelofibrosis, MPN unclassifiable, 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

You may not qualify if:

• Previous treatment with chemotherapy (e.g. hypomethylating agents or cytarabine-based regimens) for MPN with \>= 5% blasts in the blood or marrow. 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
• For patients planned to receive pacritinib, corrected QT interval (QTc) \> 480 msec (changing of medications/supplementing electrolytes is allowed to determine if this helps QTc reduce to \< 480 msec)
• For patients planned to receive pacritinib, concurrent use of medications that are CYP1A2, CYP3A4, P-gp, BCRP, OCT1 substrates that cannot be discontinued

Sponsors & Collaborators

• University of Washington: lead

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Thrombocythemia, Essential; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Leukemia, Monocytic, Acute

Interventions

Decitabine; Injections; ruxolitinib; fedratinib; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Anna Halpern

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Noah Pinke

CONTACT

206-606-4942; ntpinke@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2020
• First Posted: February 24, 2020
• Study Start: March 24, 2020
• Primary Completion (Estimated): November 11, 2026
• Study Completion (Estimated): November 11, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)