Decitabine With Ruxolitinib, Fedratinib or Pacritinib for the Treatment of Accelerated/Blast Phase Myeloproliferative Neoplasms
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
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 5 years
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "After completion of study treatment, patients are followed up for up to 5 years."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests decitabine with ruxolitinib, fedratinib, or pacritinib before a donor stem cell transplant. It is for adults with myeloproliferative neoplasms (MPNs), a group of blood cancers, that have reached a more advanced stage.
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.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- You must be 18 or older.
- You must have a history of MPN and at least 5% blasts (immature blood cells) in your blood or bone marrow. The study team must review your blood or bone marrow samples.
- You must meet the study’s limits for daily activity and ability to care for yourself.
- Your kidney test must show a creatinine clearance of at least 50 mL/min.
- Your liver tests must meet study limits. Some exceptions are allowed if results are due to MPN, Gilbert’s disease, or the breakdown of red blood cells.
- If you will take fedratinib, your thiamine (vitamin B1) level must be normal before treatment. Low levels may be treated and checked again.
- Your doctor must consider you a possible stem cell transplant candidate.
- You must be able to understand the study and give consent to join.
Who can't join
- You have had chemotherapy for MPN with at least 5% blasts. Prior hydroxyurea, interferon, JAK inhibitors, and temporary treatments to control blood counts are allowed.
- You have an active infection that is not being treated, controlled, or stable.
- You have a known allergy to any study drug.
- You are pregnant or breastfeeding.
- You received another experimental drug for MDS or leukemia within 2 weeks before starting study drugs.
- You will take fedratinib, or ruxolitinib with a platelet count below 50,000, and cannot stop certain medicines that affect how your body processes these drugs.
- You will take pacritinib and have a QTc above 480 milliseconds—a heart test result linked to heart rhythm. Medicine changes or mineral supplements may be tried to lower it.
- You will take pacritinib and cannot stop certain medicines that interact with it.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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
Study sites (1)
WA
- Fred Hutch/University of Washington Cancer Consortium · Seattle, WA 98109Noah Pinke · Study contact · 206-606-4942 · ntpinke@fredhutch.orgAnna Halpern · Principal investigatorMore trials in Seattle