Myeloproliferative DiseasesPhase 2NCT02267278
Ruxolitinib and Pracinostat Combination Therapy for Patients With Myelofibrosis (MF)
A Phase 2 study testing Ruxolitinib, Pracinostat and Questionnaire in people with Myeloproliferative Diseases, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloproliferative Diseases
- What is being tested?
- Ruxolitinib, Pracinostat and Questionnaire
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jan 2015to 1 Jun 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Evaluation of Ruxolitinib and Pracinostat Combination as a Therapy for Patients With Myelofibrosis
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.
Read the detailed description
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take ruxolitinib by mouth 2 times each day. You may take your dose of ruxolitinib with or without food.
You will also take pracinostat by mouth 1 time each day for 3 alternating days (for example Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) every 3 weeks starting on Day 1 of Cycle 4. You will take your dose of pracinostat in the morning, about 30 minutes before or 2 hours after a meal. You should swallow your dose of pracinostat whole with a cup of water (about 8 ounces).
You will be given a study drug diary to write down when you take your dose of study drugs and if you miss or vomit any doses of study drug. You must bring the diary with you to the clinic on Day 1 of each cycle and at the end-of-treatment visit. You will also need to bring any leftover pills and any empty containers of the study drugs to the clinic when the study doctor tells you to do so.
Study Visits:
There are 28 days (4 weeks) in every study cycle. You will visit MD Anderson for regular study visits while participating in this study during Cycles 2-7, and then once every 3 cycles after that (Cycles 10, 13, 16, and so on).
Once during Cycles 2-7 and then once every 3 cycles after that (Cycles 10, 13, 16, and so on):
- You will have a physical exam.
- You will complete the questionnaire about your quality of life.
At your visits during Cycles 4, 5, and 6 and then once every 3 cycles starting with cycle 10 (cycles 10, 13, 16 and so on): You will have an EKG to check your heart function.
At your visits during Cycles 4, 5, and 7 and then every 3 cycles after that (Cycles 10, 13, 16, and so on) blood (about 1-2 teaspoons) will be drawn for cytokine testing.
At your visits during Cycles 7 and 13, and then every 6 cycles after that (Cycles 19, 25, 31, and so on), if the doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease and for cytogenetic and genetic testing.
Every 2 weeks during the first 6 cycles and then about every 3 cycles after that, blood (about 2-3 tablespoons) will be drawn for routine tests. In between the mandatory visits to MD Anderson, you may choose to have these blood draws performed at a local lab or clinic closer to your home. The results will be sent to the study doctor.
Length of Treatment:
You may continue taking the study drugs for up to 4 years. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up.
Follow-Up:
About 30 days after your last dose of study drugs, if you are not receiving another treatment for MF, you will be called by the study doctor or a member of the study staff and asked about any side effects you may be having. This call should last about 10 minutes.
- Conditions
- Myeloproliferative Diseases
- Being tested
- Ruxolitinib, Pracinostat, Questionnaire
- Keywords
- Myeloproliferative Diseases, Myelofibrosis, MF, Primary or post essential thrombocythemia/polycythemia vera, Ruxolitinib, Jakafi, INCB018424, INC424, Pracinostat, Questionnaire, Survey
- Medical subject headings
- Primary Myelofibrosis, Polycythemia Vera
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called Jakafi, INCB018424, INC424
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.
PracinostatDrug
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.
QuestionnaireBehavioural
Also called Survey
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ruxolitinib; Drug: Pracinostat; Behavioral: Questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 months
Secondary outcomes (1)
Toxicity of Combination of Ruxolitinib With Pracinostat
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).
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2014 (estimated)
- Study start12 Jan 2015
- Primary completion1 Jun 2018
- Study completion1 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myeloproliferative DiseasesStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Helsinn Healthcare SA
- Responsible party
- Sponsor
- Investigators
- Srdan Verstovsek, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02267278
- Sponsor's protocol ID
- 2014-0445
- Other IDs
- NCI-2015-00002
- Status last verified
- Jun 2019
- First submitted
- 14 Oct 2014
- Last updated
- 12 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Ruxolitinib and Pracinostat Combination as a Therapy for Patients With Myelofibrosis
- ClinicalTrials.gov ID
- NCT02267278
- Acronym / sponsor ID
- 2014-0445
- Conditions
- Myeloproliferative Diseases
- Keywords
- Myeloproliferative Diseases, Myelofibrosis, MF, Primary or post essential thrombocythemia/polycythemia vera, Ruxolitinib, Jakafi, INCB018424, INC424
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Helsinn Healthcare SA
- Study start
- 12 Jan 2015 (actual)
- Primary completion
- 1 Jun 2018 (actual)
- Study completion
- 1 Jun 2018 (actual)
- First posted
- 17 Oct 2014 (estimated)
- Results
- Posted 5 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study Drug Administration:
If you are found to be eligible to take part in this study, you will take ruxolitinib by mouth 2 times each day. You may take your dose of ruxolitinib with or without food.
You will also take pracinostat by mouth 1 time each day for 3 alternating days (for example Monday, Wednesday, Friday or Tuesday, Thursday, Saturday) every 3 weeks starting on Day 1 of Cycle 4. You will take your dose of pracinostat in the morning, about 30 minutes before or 2 hours after a meal. You should swallow your dose of pracinostat whole with a cup of water (about 8 ounces).
You will be given a study drug diary to write down when you take your dose of study drugs and if you miss or vomit any doses of study drug. You must bring the diary with you to the clinic on Day 1 of each cycle and at the end-of-treatment visit. You will also need to bring any leftover pills and any empty containers of the study drugs to the clinic when the study doctor tells you to do so.
Study Visits:
There are 28 days (4 weeks) in every study cycle. You will visit MD Anderson for regular study visits while participating in this study during Cycles 2-7, and then once every 3 cycles after that (Cycles 10, 13, 16, and so on).
Once during Cycles 2-7 and then once every 3 cycles after that (Cycles 10, 13, 16, and so on):
- You will have a physical exam.
- You will complete the questionnaire about your quality of life.
At your visits during Cycles 4, 5, and 6 and then once every 3 cycles starting with cycle 10 (cycles 10, 13, 16 and so on): You will have an EKG to check your heart function.
At your visits during Cycles 4, 5, and 7 and then every 3 cycles after that (Cycles 10, 13, 16, and so on) blood (about 1-2 teaspoons) will be drawn for cytokine testing.
At your visits during Cycles 7 and 13, and then every 6 cycles after that (Cycles 19, 25, 31, and so on), if the doctor thinks it is needed, you will have a bone marrow biopsy to check the status of the disease and for cytogenetic and genetic testing.
Every 2 weeks during the first 6 cycles and then about every 3 cycles after that, blood (about 2-3 tablespoons) will be drawn for routine tests. In between the mandatory visits to MD Anderson, you may choose to have these blood draws performed at a local lab or clinic closer to your home. The results will be sent to the study doctor.
Length of Treatment:
You may continue taking the study drugs for up to 4 years. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over after the follow-up.
Follow-Up:
About 30 days after your last dose of study drugs, if you are not receiving another treatment for MF, you will be called by the study doctor or a member of the study staff and asked about any side effects you may be having. This call should last about 10 minutes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ruxolitinib + Pracinostat | Experimental | Drug: Ruxolitinib, Drug: Pracinostat, Behavioral: QuestionnaireRuxolitinib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RuxolitinibAlso: Jakafi, INCB018424, INC424Ruxolitinib 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. | Drug | Ruxolitinib + Pracinostat |
| PracinostatStarting 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. | Drug | Ruxolitinib + Pracinostat |
| QuestionnaireAlso: SurveyQuestionnaire regarding quality of life completed at baseline, within 3 days before Day 1 of Cycles 1 - 6, and then every 3 cycles after that. | Behavioural | Ruxolitinib + Pracinostat |
Primary outcome
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
1 secondary outcome
Toxicity of Combination of Ruxolitinib With Pracinostat
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Srdan Verstovsek, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib, Pracinostat and Questionnaire in people with Myeloproliferative Diseases, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2019.