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Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (MF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02267278
Recruitment Status : Completed
First Posted : October 17, 2014
Results First Posted : June 5, 2019
Last Update Posted : June 12, 2019
Helsinn Healthcare SA
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if pracinostat, when given in combination with ruxolitinib, can help to control myelofibrosis (MF). The safety of this drug combination will also be studied.

This is an investigational study. Pracinostat is not FDA-approved or commercially available. It is currently being used for research purposes only. Ruxolitinib is FDA-approved and commercially available to treat MF.

The study doctor can explain how the study drugs are designed to work.

Up to 25 participants will be enrolled in this study. All will take part at MD Anderson.

Condition or disease Intervention/treatment Phase
Myeloproliferative Diseases Drug: Ruxolitinib Drug: Pracinostat Behavioral: Questionnaire Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Ruxolitinib and Pracinostat Combination as a Therapy for Patients With Myelofibrosis
Actual Study Start Date : January 12, 2015
Actual Primary Completion Date : June 1, 2018
Actual Study Completion Date : June 1, 2018

Arm Intervention/treatment
Experimental: Ruxolitinib + Pracinostat

Ruxolitinib starting dose 15 mg orally twice/day in 28-day cycle (dose assigned based on platelet count, if low platelet count gradual up-titration from a starting dose of 5 mg) - given alone for first 3 months, then Pracinostat added at starting dose 60 mg orally once/day for 3 alternating days every 3 weeks starting Day 1 of Cycle 4.

Dose of Ruxolitinib may be increased or decreased prior to initiation of Pracinostat. Quality of Life Questionnaire.

Drug: Ruxolitinib
Ruxolitinib taken by mouth 2 times each day in a 28-day cycle. Patients receive Ruxolitinib alone for first 3 months, and then Pracinostat added. Starting dose of Ruxolitinib based on patients' platelet count. Dose of Ruxolitinib may be increased or decreased at discretion of treating physician prior to initiation of Pracinostat.
Other Names:
  • Jakafi
  • INCB018424
  • INC424

Drug: Pracinostat
Starting dose of Pracinostat 60 mg by mouth 1 time each day for 3 alternating days every 3 weeks starting on Day 1 of Cycle 4.

Behavioral: Questionnaire
Questionnaire regarding quality of life completed at baseline, within 3 days before Day 1 of Cycles 1 - 6, and then every 3 cycles after that.
Other Name: Survey

Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 3 months ]
    Objective response rate (ORR), defined as a clinical improvement (CI), partial remission (PR), and complete remission (CR) according to the International Working Group (IWG) Criteria. Complete remission (CR): bone marrow blasts <5%, hemoglobin >/= 10, absolute neutrophil count (ANC) >/= 1000, platelets >/= 100, <2% immature myeloid cell, spleen and liver not palpable. Partial Response (PR): CR plus one or more of the following: ANC >/= 1000, decreased platelets by 50%, hemoglobin >/= 8.5 but < 10, <2% immature myeloid cells. Clinical improvement (CI): hemoglobin increase of 2g/dl, transfusion independence or reduction splenomegaly and/or hepatomegaly >/= 50%, >/=50% reduction in MPN-SAF TSS

Secondary Outcome Measures :
  1. Toxicity of Combination of Ruxolitinib With Pracinostat [ Time Frame: 3 months ]
    Toxicity defined as Grade 3-4 clinically relevant non-hematologic toxicity or a serious adverse event that is at least possibly related to the study drug (Common Terminology Criteria for Adverse Events CTCAE version 4.0).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Diagnosis of MF (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk according to International Prognostic Scoring System (IPSS).
  2. Palpable splenomegaly of more than or equal to 5 cm below left costal margin on physical exam
  3. Understanding and voluntary signing an Institutional Review Board (IRB)-approved informed consent form.
  4. Age equal to or more than 18 years at the time of signing the informed consent.
  5. Disease-free of other malignancies.
  6. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
  7. Negative pregnancy test in females of childbearing potential (FCBP). Male patients with female partners of child-bearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 30 days following last dose. Acceptable forms of contraception include 1 highly effective method such as an intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation, or partner's vasectomy and at least 1 additional approved barrier method such as a latex condom, diaphragm, or cervical cap. Female patients of childbearing potential must not be breast-feeding or planning to breast feed and must have a negative pregnancy test ≤7 days before first study treatment.
  8. QTcF interval equal to or less than 470 msec
  9. Normal serum potassium magnesium levels
  10. Adequate organ function as demonstrated by the following: Direct bilirubin equal to or less than 2.0 mg/dL, Serum creatinine equal to or less than 2.0 mg/dL., Alanine transaminase (SGPT) equal to or less than 3 x upper limit of normal (unless considered to be related to MF or patient has known history of Gilberts)
  11. Platelets >/= 50000/uL
  12. Absolute Neutrophil count (ANC) >/= 1000/uL

Exclusion Criteria:

  1. Prior therapy with a JAK inhibitor (other than ruxolitinib for less than 3 months duration and currently on it) or HDACi. Patients that are currently on ruxolitinib for less than 3 months of therapy are eligible.
  2. Use of any other standard or experimental therapy within 14 days of starting study therapy.
  3. Lack of recovery from all toxicity from previous therapy to grade 1 or baseline.
  4. Suspected pregnancy, pregnant or lactating females.
  5. Any condition, including the presence of laboratory abnormalities, which in the opinion of the treating physician 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.
  6. Known positive for HIV or infectious hepatitis, type A, B or C.
  7. Patients with gastrointestinal (GI) tract disease, causing the inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's disease, ulcerative colitis)
  8. Cardiopulmonary function criteria: • Current unstable arrhythmia requiring treatment • History of symptomatic congestive heart failure • History of myocardial infarction within 6 months of enrollment • Current unstable angina • Family history of long QT syndrome

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02267278

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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Helsinn Healthcare SA
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Principal Investigator: Srdan Verstovsek, MD M.D. Anderson Cancer Center
  Study Documents (Full-Text)

Documents provided by M.D. Anderson Cancer Center:
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT02267278    
Other Study ID Numbers: 2014-0445
NCI-2015-00002 ( Registry Identifier: NCI CTRP )
First Posted: October 17, 2014    Key Record Dates
Results First Posted: June 5, 2019
Last Update Posted: June 12, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Myeloproliferative Diseases
Primary or post essential thrombocythemia/polycythemia vera
Additional relevant MeSH terms:
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Primary Myelofibrosis
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases