Trial Outcomes & Findings for Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (MF) (NCT NCT02267278)

Last Updated: 2019-06-12

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

3 months

Results posted on

2019-06-12

Participant Flow

Recruitment Period: January 2015 to March 2017

Of the twenty-five participants who started the study, five never began pracinostat and are not considered evaluable for response.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	25
Overall Study COMPLETED	20
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Proceeded to transplantation (allo-HCT)	1
Overall Study transformation to acute leukemia (AML)	1
Overall Study Developed new cancer diagnoses	2
Overall Study prescribed prohibited medication	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ruxolitinib + Pracinostat n=25 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	15 Participants n=5 Participants
Age, Continuous	67 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Outcome measures

Outcome measures
Measure	Ruxolitinib + Pracinostat n=20 Participants 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.
Objective Response Rate (ORR)	16 Participants

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Ruxolitinib + Pracinostat n=20 Participants 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.
Toxicity of Combination of Ruxolitinib With Pracinostat	1 Participants

Adverse Events

Ruxolitinib + Pracinostat

Serious events: 8 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ruxolitinib + Pracinostat n=25 participants at risk 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.
Renal and urinary disorders Benign Mass Kidney	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Infections and infestations Bronchial Infection	4.0% 1/25 • Number of events 2 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Cardiac disorders Chest Pain - Cardiac	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Infections and infestations Infection	8.0% 2/25 • Number of events 4 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Cardiac disorders Conduction disorder	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Gastrointestinal disorders Diarrhea	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
General disorders Fatigue	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
General disorders Fever	8.0% 2/25 • Number of events 2 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Musculoskeletal and connective tissue disorders Fracture	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Cardiac disorders Heart failure	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Vascular disorders Hypotension	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Blood and lymphatic system disorders Thrombocytopenia	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Respiratory, thoracic and mediastinal disorders Pleuritic Pain	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Surgical and medical procedures Stent placement	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Surgical and medical procedures Total Aurilectomy	4.0% 1/25 • Number of events 1 • up to three years All 25 participants registered on this study were evaluable for adverse events.

Other adverse events

Other adverse events
Measure	Ruxolitinib + Pracinostat n=25 participants at risk 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.
General disorders Abdominal pain	12.0% 3/25 • Number of events 3 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Blood and lymphatic system disorders Anemia	68.0% 17/25 • Number of events 17 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Investigations Elevated Liver Function Tests	8.0% 2/25 • Number of events 2 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Gastrointestinal disorders Diarrhea	16.0% 4/25 • Number of events 4 • up to three years All 25 participants registered on this study were evaluable for adverse events.
General disorders Fatigue	32.0% 8/25 • Number of events 8 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Gastrointestinal disorders Flatulence	20.0% 5/25 • Number of events 5 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Blood and lymphatic system disorders Leukocytosis	8.0% 2/25 • Number of events 2 • up to three years All 25 participants registered on this study were evaluable for adverse events.
General disorders Malaise	8.0% 2/25 • Number of events 2 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Gastrointestinal disorders Nausea	12.0% 3/25 • Number of events 3 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Skin and subcutaneous tissue disorders Shingles	16.0% 4/25 • Number of events 4 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Blood and lymphatic system disorders Thrombocytopenia	52.0% 13/25 • Number of events 13 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Investigations Weight gain	16.0% 4/25 • Number of events 4 • up to three years All 25 participants registered on this study were evaluable for adverse events.
Blood and lymphatic system disorders Leukopenia	24.0% 6/25 • Number of events 6 • up to three years All 25 participants registered on this study were evaluable for adverse events.

Additional Information

Srdan Verstovsek, MD/Professor

The University of Texas MD Anderson Cancer Center

Phone: 713-745-3429

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place