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Trial record 1 of 2 for:    Panobinostat and Ruxolitinib in myelofibrosis
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Panobinostat and Ruxolitinib In MyElofibrosis (PRIME Trial) (PRIME)

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ClinicalTrials.gov Identifier: NCT01693601
Recruitment Status : Active, not recruiting
First Posted : September 26, 2012
Last Update Posted : February 13, 2018
Sponsor:
Information provided by (Responsible Party):
John Mascarenhas, Icahn School of Medicine at Mount Sinai

September 14, 2012
September 26, 2012
February 13, 2018
January 2013
February 2019   (Final data collection date for primary outcome measure)
  • number of patients that experience adverse events [ Time Frame: at least 28 days ]
    Assess the safety and tolerability of Ruxolitinib in combination with Panobinostat in patients with MF
  • proportion of patients that achieve at least stable disease [ Time Frame: at least 6 months ]
    Assess treatment response as defined by the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)
Same as current
Complete list of historical versions of study NCT01693601 on ClinicalTrials.gov Archive Site
  • Spleen size [ Time Frame: up to 14 months ]
    Assess changes in spleen size by palpation and MRI
  • exploratory biomarkers [ Time Frame: up to 14 months ]
    o evaluate changes in inflammatory cytokines to therapy
  • symptom response [ Time Frame: at least 6 months ]
    Assess symptom response with a validated MPN tool (MPN-SAF)
Same as current
Not Provided
Not Provided
 
Panobinostat and Ruxolitinib In MyElofibrosis (PRIME Trial)
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.
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.
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Myelofibrosis
  • Drug: Panobinostat
    PO TIW QOW or PO TIW QW
    Other Name: LBH589
  • Drug: Ruxolitinib
    PO BID x 28 days
    Other Name: INCB424, Jakafi
Experimental: Panobinostat and Ruxolitinib
Combination of Panobinostat and Ruxolitinib
Interventions:
  • Drug: Panobinostat
  • Drug: Ruxolitinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
18
58
February 2019
February 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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

    1. Chronic Phase (MF-CP)
    2. Accelerated Phase (MF-AP)
  • Patients must meet the following laboratory criteria:

    1. ANC ≥ .750 x 109/L
    2. Platelets ≥ 75 x 109/L
    3. Creatinine ≤ 1.5 x ULN,
    4. AST and ALT ≤ 2.5 x ULN
    5. Serum bilirubin ≤ 1.5 x ULN (unless Gilbert's syndrome and evidence of hemolysis)
    6. Serum potassium ≥ LLN
    7. Total serum calcium [corrected for serum albumin] or ionized calcium ≥LLN,
    8. Serum magnesium ≥ LLN
    9. Serum phosphorus ≥ LLN
    10. 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

Exclusion Criteria:

  • 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:

    1. With permanent cardiac pacemaker
    2. Resting bradycardia defined as <50 beats per minute
    3. QTcF >450 msec on screening ECG
    4. Complete Left bundle branch block, bifascicular block
    5. Any clinically significant ST segment and/or T-wave abnormalities
    6. 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.
    7. 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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01693601
GCO 12-1225
Yes
Not Provided
Not Provided
John Mascarenhas, Icahn School of Medicine at Mount Sinai
John Mascarenhas
Not Provided
Principal Investigator: John Mascarenhas, MD Icahn School of Medicine at Mount Sinai
Icahn School of Medicine at Mount Sinai
February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP