A Study to Compare the Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects with Myelofibrosis who were Treated with Ruxolitinib
- Conditions
- Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis.MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-005007-13-GB
- Lead Sponsor
- Sierra Oncology, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 150
1) Age = 18 years old
2) Palpable splenomegaly at least 5 cm below left costal margin
3) Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) criteria, or Post-PV/ET MF in accordance with the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria
4) Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days and characterized by:
- Requirement for red blood cell (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:
* = CTCAE Grade 3 thrombocytopenia, OR
* = CTCAE Grade 3 anemia, OR
* = CTCAE Grade 3 hematoma (bleed)
5) 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
6) 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
7) If not receiving therapy for myelofibrosis, must remain off therapy for at least 2 weeks prior to screen date and through the screening period
8) Acceptable laboratory assessment 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%
- AST/SGOT and ALT/SGPT = 3 x 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
9) Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
10) Life expectancy > 24 weeks
11) Negative serum pregnancy test for female subjects (unless surgically sterile or greater than 2 years post-menopausal)
12) Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
13) Females who are nursing must agree to discontinue nursing before the first dose of MMB
14) Able to understand and willing to sign informed consent form (ICF)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1) Prior splenectomy
2) Splenic irradiation within 3 months prior to randomization
3) Use of investigational agent within 28 days prior to randomization
4) Prior treatment with MMB
5) Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) within 28 days prior to Day 1
6) Uncontrolled intercurrent illness including, but not limited to: active uncontrolled infection (subjects receiving outpatient antibacterial and/or antiviral treatments for infection that is under control or as infection prophylaxis may be included in the study); active or chronic bleeding event within 4 weeks prior to randomization; symptomatic congestive heart failure (CHF); unstable angina pectoris; uncontrolled cardiac arrhythmia; or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician
7) QTc interval > 450 msec, unless attributed to bundle branch block
8) History of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for = 1 year prior to randomization, adequately treat Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for = 5 years
9) Known positive status for human immunodeficiency virus (HIV)
10) Chronic active or acute viral hepatitis A. B or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
11) Unresolved non-hematologic toxicities from prior therapies that are > CTCAE Grade 1
12) Use of CYP3A4 inducers within 1 week prior to randomization
13) Changes to dose of iron chelator therapy within 14 days prior to randomization
14) Presence of peripheral neuropathy = CTCAE Grade 2
15) Unwilling or unable to undergo a MRI or CT Scan
16) Known hypersensitivity to MMB, the metabolites, or formulation excipients
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method