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MyelofibrosisPhase 1/2PRIMENCT01693601

Panobinostat and Ruxolitinib In MyElofibrosis (PRIME Trial)

A Phase 1/2 study testing Panobinostat and Ruxolitinib in people with Myelofibrosis, run by John Mascarenhas at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a single-center, single arm, dose finding study to assess safety and tolerability of the oral combination of Panobinostat and Ruxolitinib in patients with myelofibrosis (MF) in chronic and accelerated phase. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelofibrosis
What is being tested?
Panobinostat and Ruxolitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
Jan 2013to 18 May 2018
Phase
Phase 1/2
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

  • Male or female patients aged ≥ 18 years old
  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • Intermediate-2 and higher by IWG-MRT Post PV/ET MF and PMF patients either in
  • Chronic Phase (MF-CP)
  • Accelerated Phase (MF-AP)
  • Patients must meet the following laboratory criteria:
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  • ANC ≥ .750 x 109/L
  • Platelets ≥ 75 x 109/L
  • Creatinine ≤ 1.5 x ULN,
  • AST and ALT ≤ 2.5 x ULN
  • Serum bilirubin ≤ 1.5 x ULN (unless Gilbert's syndrome and evidence of hemolysis)
  • Serum potassium ≥ LLN
  • Total serum calcium [corrected for serum albumin] or ionized calcium ≥LLN,
  • Serum magnesium ≥ LLN
  • Serum phosphorus ≥ LLN
  • Free T4 within normal limits
  • ECOG Performance Status of ≤ 3
  • Any prior therapy with JAK2-TKI, hypomethylating agents, HDACI, mTORi, or iMiDs is allowed as long as it is greater than 3 weeks since last dose of administration and in the case of a JAK2-TKI or HDACI that discontinuation was not due to non-hematologic drug toxicity. An exception to this criteria are patients currently on at least 10mg BID of ruxolitinib for greater than 3 months and who have not shown an optimal response (i.e. without 50% reduction in palpable splenomegaly or 50% reduction in symptom burden). With a reduction of ruxolitinib to 10mg BID these patients may enter onto the study without stopping ruxolitinib

Who cannot join

  • Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first PANOBINOSTAT treatment.
  • Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
  • With permanent cardiac pacemaker
  • Resting bradycardia defined as <50 beats per minute
  • QTcF >450 msec on screening ECG
  • Complete Left bundle branch block, bifascicular block
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  • Any clinically significant ST segment and/or T-wave abnormalities
  • Presence of unstable atrial fibrillation (ventricular response rate >100 bpm). Patients with stable atrial fibrillation can be enrolled provided they do not meet other cardiac exclusion criteria.
  • Symptomatic congestive heart failure (NYHA class III-IV)
  • Impairment of GI function or GI disease that may significantly alter the absorption of PANOBINOSTAT or RUXOLITINIB
  • Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes or active or uncontrolled infection) including abnormal laboratory values, that could cause unacceptable safety risks or compromise compliance with the protocol
  • Patients using medications that have a relative risk of prolonging the QT interval or inducing torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Concomitant use of CYP3A4 inhibitors
  • Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies.
  • Chemotherapy within 3 weeks prior to screening are excluded (other than hydroxyurea at stable doses and will be discontinued 24 hours prior to starting study drug).
  • Patients with an active bleeding tendency or are receiving any treatment with therapeutic doses of sodium warfarin (Coumadin®) or coumadin derivatives. Patients will be allowed to enter study on aspirin at doses of 81mg/d.
  • Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Women who are pregnant or breast-feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test within 24hrs of receiving the first dose of study medication.
  • Male patients whose sexual partners are WOCBP not using effective birth control
  • Patients with a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix)
  • Disease associated with secondary MF such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease or acute leukemia (including M7 disease or acute panmyelosis with MF)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Official title: Panobinostat and Ruxolitinib In MyElofibrosis (PRIME STUDY) - Phase I/II Study of Combination Oral JAK2 Tyrosine Kinase Inhibitor (JAK2-TKI) and Histone Deacetylase Inhibitor (HDACI) Therapy in Patients With Myelofibrosis

This is a single-center, single arm, dose finding study to assess safety and tolerability of the oral combination of Panobinostat and Ruxolitinib in patients with myelofibrosis (MF) in chronic and accelerated phase.

Read the detailed description

Phase I/II open label, single institution, combination therapy trial of induction Ruxolitinib followed by combination with Panobinostat in dose escalation cohorts with a primary endpoint of determining the safety and tolerability of combination therapy in patients with myelofibrosis (MF) in chronic and accelerated phase. A 3+3standard dose escalation scheme will be employed and the occurrence of dose limiting toxicities (DLTs) will be captured and the occurrence of such events will determine dose cohort escalation by predetermined and established rules. In addition to establishing the DLTs, maximally tolerated dose (MTD), and recommended phase II dose (RPTD) in the phase I portion of this trial, exploratory biomarkers will be evaluated within phase I as well. Pharmacodynamics and exploratory genetic and epigenetic biomarkers will be explored as predictors of response to therapy. The RPTD cohort will be expanded to incorporate a total of 22 patients, including 6 from phase I, in order to assess clinical response as assessed by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) as a primary endpoint for the phase II portion of this trial.

Conditions
Myelofibrosis
Being tested
Panobinostat, Ruxolitinib
Keywords
Myelofibrosis, Panobinostat, Ruxolitinib
Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PanobinostatDrug

    Also called LBH589

    PO TIW QOW or PO TIW QW

  • RuxolitinibDrug

    Also called INCB424, Jakafi

    PO BID x 28 days

Study groups in NCT01693601
Study groupRoleWhat they receive
Panobinostat and RuxolitinibExperimentalCombination of Panobinostat and Ruxolitinib
Receives: Drug: Panobinostat; Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients That Achieve Stable Disease or Clinical Improvement

    Number of patients that have either stable disease or clinical improvement treatment response as defined by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT).

    Stable disease (SD) - response that is not complete remission, partial remission, clinical improvement, anemia response, spleen response, symptoms response, or progressive disease.

    Clinical improvement (CI) - a response in anemia, splenomegaly, or MF-SB that is not associated with progressive splenomegaly or increase in severity of anemia, thrombocytopenia, or neutropenia.

    Measured: at least 6 months

  2. Number of Participants Who Experienced Dose-Limiting (DLTs)

    Panobinostat related adverse events requiring dose reduction or discontinuing prior to Cycle 6, Day 29 (C6D29)

    Measured: up to cycle 6, day 29

Secondary outcomes (4)

  1. Percent Change in Spleen Volume

    Percent change in spleen volume at C6D29 as compared to baseline

    Measured: Baseline and Cycle 6, Day 29

  2. Percent Change in Spleen Size for Responders and Non-responders

    Percent change in spleen length size by palpation at cycle 6, day 29 (C6D29) from baseline

    Measured: Cycle 6, Day 29

  3. Percent Change in Spleen Length

    Percent change in spleen length at C6D29

    Measured: Cycle 6, Day 29

  4. Number of Participants With Percent Change on Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF)

    Symptom responders defined as having a percent change in MPN-SAF score from Screening/C1D1 to C6D29 of more than 50%.MPN-SAF is an 18-item instrument. Each item score 0-10 averaged, total scale from0-10, with higher score indicating more symptoms.

    Measured: baseline, C1D1 and Cycle 6 Day 29

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Sep 2012 (estimated)
  2. Study startJan 2013
  3. Primary completion18 May 2018
  4. Study completion18 May 2018

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01693601
Sponsor's protocol ID
GCO 12-1225
Acronym
PRIME
Status last verified
Oct 2023
First submitted
14 Sep 2012
Last updated
31 Oct 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Mascarenhas J, Marcellino BK, Lu M, Kremyanskaya M, Fabris F, Sandy L, Mehrotra M, Houldsworth J, Najfeld V, El Jamal S, Petersen B, Moshier E, Hoffman R. A phase I study of panobinostat and ruxolitinib in patients with primary myelofibrosis (PMF) and post--polycythemia vera/essential thrombocythemia myelofibrosis (post--PV/ET MF). Leuk Res. 2020 Jan;88:106272. doi: 10.1016/j.leukres.2019.106272. Epub 2019 Nov 16.

    PubMed 31778911

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Panobinostat and Ruxolitinib in people with Myelofibrosis, run by John Mascarenhas 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 18 inclusion and 21 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 31 Oct 2023. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 31 Oct 2023). 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?

Number of Patients That Achieve Stable Disease or Clinical Improvement (time frame: at least 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01693601, which also lists 1 linked publication.

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 31 Oct 2023.

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