Clinical trial NCT02101268: Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF
Official title: A Phase 3, Randomized Study To Evaluate the Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis Who Were Treated With Ruxolitinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Myelofibrosis (PMF)
Post-polycythemia Vera (Post-PV)
Post-essential Thrombocythemia Myelofibrosis (Post-ET MF)
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2014-04-02
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to determine the efficacy of momelotinib (MMB) versus best available therapy (BAT) in anemic or thrombocytopenic adults with primary myelofibrosis (PMF), or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/ET MF) who were treated with ruxolitinib as measured by splenic response rate at Week 24 (SRR24).

Participants will be randomized to receive either MMB or BAT for 24 weeks during the randomized treatment phase, after which they will be eligible to receive MMB in an extended treatment phase for up to an additional 204 weeks. After discontinuation of study medication, assessments will continue for 12 additional weeks, after which participants will be contacted for survival follow-up approximately every 6 months for up to 5 years from the date of enrollment or until study termination. For those subjects planning to continue treatment with MMB following the end of the study, the End of Treatment, 30-day, 12-Week, and survival follow-up visits are not required.


Eligibility criteria: Key Inclusion Criteria:

* Palpable splenomegaly at least 5 cm below left costal margin
* Confirmed diagnosis of PMF in accordance, or Post-PV/ET MF
* Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days, and characterized by

  * Requirement for RBC transfusion while on ruxolitinib treatment, OR
  * Dose adjustment of ruxolitinib to \< 20 mg twice daily at start of or during ruxolitinib treatment AND at least one of the following while on ruxolitinib treatment:

    * ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 thrombocytopenia, OR
    * ≥ CTCAE Grade 3 anemia, OR
    * ≥ CTCAE Grade 3 hematoma (bleed)
* High risk OR intermediate-2 risk as defined by Dynamic International Prognostic Scoring System (DIPSS), OR intermediate-1 risk as defined by DIPSS and associated with symptomatic splenomegaly, and/or hepatomegaly
* If receiving myelofibrosis therapy, must be on a stable dose of the same regimen for at least 2 weeks prior to screen date and through the screening period
* If not receiving myelofibrosis therapy, must remain off therapy for at least 2 weeks prior to screen date and through the screening period
* Acceptable laboratory assessments obtained within 14 days prior to Randomization

  * Absolute neutrophil count (ANC) \> 0.75 x 10\^9/L in the absence of growth factor in the prior 7 days
  * Peripheral blood blast count \< 10%
  * Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the upper limit of the normal range (ULN) (≤ 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
  * Calculated creatinine clearance of ≥ 45 mL/min
  * Direct bilirubin ≤ 2.0 x ULN
* Life expectancy \> 24 weeks
* Negative serum pregnancy test for female subjects (unless surgically sterile or greater than two years post-menopausal)
* Males and females of childbearing potential must agree to use protocol-specified method(s) of contraception
* Females who are nursing must agree to discontinue nursing before the first dose of MMB
* Able to understand and willing to sign informed consent form (ICF)

Key Exclusion Criteria:

* Prior splenectomy
* Splenic irradiation within 3 months prior to Randomization
* Use of investigational agent within 28 days prior to Randomization
* Prior treatment with MMB
* Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) within 28 days prior to Randomization
* Uncontrolled inter-current illness, per protocol
* Known positive status for human immunodeficiency virus (HIV)
* Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier
* Presence of peripheral neuropathy ≥ CTCAE Grade 2
* Unwilling or unable to undergo a MRI or CT Scan per study protocol requirements

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Splenic Response Rate at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Total Symptom Score (TSS) Response Rate at Week 24
timeFrame: Week 24
measure: Rate of Red Blood Cell (RBC) Transfusion in the Randomized Treatment Phase, (the Average Number of RBC Units Transfused Per Month Not Associated With Overt Bleeding)
timeFrame: Baseline to Week 24
measure: RBC Transfusion Independence Rate at Week 24, (Defined as Absence of RBC Transfusions and no Hemoglobin Level Below 8 g/dL in the 12 Weeks Prior to Week 24, Excluding Cases Associated With Clinically Overt Bleeding)
timeFrame: Week 24
measure: RBC Transfusion Dependence Rate at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Gainesville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Kansas City
country: United States
state: Kansas
city: Baltimore
country: United States
state: Maryland
city: Saint Louis
country: United States
state: Missouri
city: Albuquerque
country: United States
state: New Mexico
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Pittsburgh
country: United States
state: Pennsylvania
city: Houston
country: United States
state: Texas
city: Edmonton
country: Canada
state: Alberta
city: Montreal
country: Canada
city: Toronto
country: Canada
city: Lille cedex
country: France
city: Marseille
country: France
city: Nantes
country: France
city: Paris
country: France
city: Pierre Benite Cedex
country: France
city: Toulouse
country: France
city: Villejuif Cedex
country: France
city: Dresden
country: Germany
city: Hamburg
country: Germany
city: Koln
country: Germany
city: Mannheim
country: Germany
city: Ashkelon
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Tel-Aviv
country: Israel
city: Bologna
country: Italy
city: Firenze
country: Italy
city: Genova
country: Italy
city: Milano
country: Italy
city: Novara
country: Italy
city: Roma
country: Italy
city: Varese
country: Italy
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Salamanca
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Birmingham
country: United Kingdom
state: England
city: Leeds
country: United Kingdom
state: England
city: Leicester
country: United Kingdom
state: England
city: London
country: United Kingdom
state: England
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Harrison CN, Vannucchi AM, Platzbecker U, Cervantes F, Gupta V, Lavie D, Passamonti F, Winton EF, Dong H, Kawashima J, Maltzman JD, Kiladjian JJ, Verstovsek S. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018 Feb;5(2):e73-e81. doi: 10.1016/S2352-3026(17)30237-5. Epub 2017 Dec 20.