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

NCT02267278 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2014-0445NCI-2015-00002
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Myeloproliferative Diseases

Keywords

Myeloproliferative Diseases; Myelofibrosis; MF; Primary or post essential thrombocythemia/polycythemia vera; Ruxolitinib; Jakafi; INCB018424; INC424; Pracinostat; Questionnaire; Survey

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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

  3 months

Secondary Outcomes (1)

• Toxicity of Combination of Ruxolitinib With Pracinostat

  3 months

Study Arms (1)

Ruxolitinib + Pracinostat

EXPERIMENTAL

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; Drug: Pracinostat; Behavioral: Questionnaire

Interventions

Ruxolitinib DRUG

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.

Also known as: Jakafi, INCB018424, INC424

Ruxolitinib + Pracinostat

Pracinostat DRUG

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.

Ruxolitinib + Pracinostat

Questionnaire BEHAVIORAL

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.

Also known as: Survey

Ruxolitinib + Pracinostat

Eligibility Criteria

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

You may qualify if:

• 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).
• Palpable splenomegaly of more than or equal to 5 cm below left costal margin on physical exam
• Understanding and voluntary signing an Institutional Review Board (IRB)-approved informed consent form.
• Age equal to or more than 18 years at the time of signing the informed consent.
• Disease-free of other malignancies.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
• 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.
• QTcF interval equal to or less than 470 msec
• Normal serum potassium magnesium levels
• 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)
• Platelets \>/= 50000/uL
• Absolute Neutrophil count (ANC) \>/= 1000/uL

You may not qualify if:

• 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.
• Use of any other standard or experimental therapy within 14 days of starting study therapy.
• Lack of recovery from all toxicity from previous therapy to grade 1 or baseline.
• Suspected pregnancy, pregnant or lactating females.
• 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.
• Known positive for HIV or infectious hepatitis, type A, B or C.
• 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)
• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Helsinn Healthcare SA: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Primary Myelofibrosis; Polycythemia Vera

Interventions

ruxolitinib; SB939 compound; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Srdan Verstovsek, MD/Professor
• Organization: The University of Texas MD Anderson Cancer Center

sverstov@mdanderson.org

713-745-3429

Study Officials

• Srdan Verstovsek, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: October 14, 2014
• First Posted: October 17, 2014
• Study Start: January 12, 2015
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: June 12, 2019
• Results First Posted: June 5, 2019

Record last verified: 2019-06

Locations

US (1)