A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Patients (MOMENTUM)

  • STATUS
    Recruiting
  • End date
    Apr 11, 2028
  • participants needed
    180
  • sponsor
    Sierra Oncology, Inc.
Updated on 11 April 2021
platelet count
stem cell transplantation
anemia
myelofibrosis
myeloproliferative disorder
direct bilirubin
investigational drug
thrombocytopenia
blast cells
neutrophil count
conjugated bilirubin
myeloproliferative neoplasm
essential thrombocythemia
thrombocytosis
polycythemia
extramedullary hematopoiesis
janus kinase inhibitor
momelotinib
blood blast count
thrombocythemia

Summary

MOMENTUM is a randomized, double-blind, active control Phase 3 trial intended to confirm the differentiated clinical benefits of the investigational drug momelotinib (MMB) versus danazol (DAN) in symptomatic and anemic subjects who have previously received an approved Janus kinase inhibitor (JAKi) therapy for myelofibrosis (MF). The purpose of this clinical study is to compare the effectiveness and safety of MMB to DAN in treating and reducing: 1) disease related symptoms, 2) the need for blood transfusions and 3) splenomegaly, in adults with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The study is planned in countries including, but not limited to: Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Israel, Italy, New Zealand, Poland, Romania, Singapore, South Korea, Spain, Sweden, Taiwan, UK, and US.

Subjects must be symptomatic with a MFSAF v4.0 Total Symptom Score of 10 at screening, and be anemic with Hgb < 10 g/dL. For subjects with ongoing JAKi therapy at screening, JAKi therapy must be tapered over a period of at least 1 week, followed by a 2-week non-treatment washout interval prior to randomization.

Subjects will be randomized 2:1 to orally self-administer blinded treatment: MMB plus placebo or DAN plus placebo. Subjects randomized to receive MMB who complete the randomized treatment period to the end of Week 24 may continue to receive MMB in the open-label extended treatment period to the end of Week 204 (a total period of treatment of approximately 4 years) if the subject tolerates and continues to benefit from MMB.

Subjects randomized to receive DAN may cross-over to MMB open-label treatment in the following circumstances:

  • at the end of Week 24 if they complete the randomized treatment period; or
  • at the end of Week 24 if they discontinue treatment with DAN but continue study assessments and do not receive prohibited medications including alternative active anti-MF therapy; or
  • at any time during the randomized treatment period if they meet the protocol-defined criteria for radiographically-confirmed symptomatic splenic progression.

Subjects randomized to receive DAN who are receiving clinical benefit at the end of Week 24 may choose to continue DAN therapy up to Week 48. The comparator treatment, DAN, is an approved medication in the US and in some other countries and is recommended by national guidelines as a treatment for anemia in MF.

Details
Condition Myelosclerosis with myeloid metaplasia, Post-PV MF, Post Essential Thrombocythemia Myelofibrosis, Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post Polycythemia Vera Myelofibrosis
Treatment Danazol, Momelotinib, Placebo to match momelotinib, Placebo to match danazol
Clinical Study IdentifierNCT04173494
SponsorSierra Oncology, Inc.
Last Modified on11 April 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Do you have any of these conditions: Post-polycythemia Vera Myelofibrosis or Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post Essential Thrombocythemia Myelofibrosis or Pos...?
Do you have any of these conditions: Post Essential Thrombocythemia Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Myelofibrosis or Myelosclerosis with myeloid metaplasia or Pos...?
Do you have any of these conditions: Post-polycythemia Vera Myelofibrosis or Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Post Essential Thrombocythemia Myelofibrosis or Myelo...?
Do you have any of these conditions: Myelosclerosis with myeloid metaplasia or Post Essential Thrombocythemia Myelofibrosis or Myelofibrosis or Post-PV MF or Post-polycythemia Vera Myelof...?
Do you have any of these conditions: Post-PV MF or Post-polycythemia Vera Myelofibrosis or Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Post Essential Thrombocythemia Myelofib...?
Do you have any of these conditions: Post-polycythemia Vera Myelofibrosis or Post Essential Thrombocythemia Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Myelofibrosis or Myelo...?
Do you have any of these conditions: Myelofibrosis or Post-polycythemia Vera Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post-PV MF or Post Polycythemia Vera Myelofibrosis ...?
Do you have any of these conditions: Post Polycythemia Vera Myelofibrosis or Post-PV MF or Post-polycythemia Vera Myelofibrosis or Post Essential Thrombocythemia Myelofibrosis or Myeloscl...?
Do you have any of these conditions: Post Essential Thrombocythemia Myelofibrosis or Post-polycythemia Vera Myelofibrosis or Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Myelo...?
Do you have any of these conditions: Post Essential Thrombocythemia Myelofibrosis or Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post-PV MF or Post Polycythemia Vera Myelof...?
Do you have any of these conditions: Myelofibrosis or Post-PV MF or Myelosclerosis with myeloid metaplasia or Post-polycythemia Vera Myelofibrosis or Post Polycythemia Vera Myelofibrosis ...?
Do you have any of these conditions: Post-PV MF or Post-polycythemia Vera Myelofibrosis or Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post Polycythemia Vera Myelofibrosis ...?
Do you have any of these conditions: Myelosclerosis with myeloid metaplasia or Post-polycythemia Vera Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Post Essential Thrombocythem...?
Do you have any of these conditions: Post-polycythemia Vera Myelofibrosis or Post-PV MF or Myelosclerosis with myeloid metaplasia or Post Essential Thrombocythemia Myelofibrosis or Post P...?
Do you have any of these conditions: Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post-PV MF or Post-polycythemia Vera Myelofibrosis or Post Polycythemia Vera Myelofibrosis ...?
Is your age greater than or equal to 18 yrs?
Do you have any of these conditions: Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post Essential Thrombocythemia Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Pos...?
Do you have any of these conditions: Post Essential Thrombocythemia Myelofibrosis or Myelofibrosis or Post-PV MF or Post-polycythemia Vera Myelofibrosis or Post Polycythemia Vera Myelofib...?
Do you have any of these conditions: Post Essential Thrombocythemia Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post-PV MF or Myelof...?
Do you have any of these conditions: Post-PV MF or Post Polycythemia Vera Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post-polycythemia Vera Myelofibrosis or Myelofibrosis ...?
Do you have any of these conditions: Post-PV MF or Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post Polycythemia Vera Myelofibrosis or Post Essential Thrombocythemia Myelof...?
Do you have any of these conditions: Post-PV MF or Myelosclerosis with myeloid metaplasia or Post Polycythemia Vera Myelofibrosis or Myelofibrosis or Post Essential Thrombocythemia Myelof...?
Do you have any of these conditions: Post Essential Thrombocythemia Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post-PV MF or Post-p...?
Do you have any of these conditions: Post-PV MF or Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post-polycythemia Vera Myelofibrosis or Post Polycythemia Vera Myelofibrosis ...?
Do you have any of these conditions: Myelosclerosis with myeloid metaplasia or Post-polycythemia Vera Myelofibrosis or Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Post Essent...?
Do you have any of these conditions: Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post Polycythemia Vera Myelofibrosis or Post-PV MF or Post-polycythemia Vera Myelofibrosis ...?
Do you have any of these conditions: Post Essential Thrombocythemia Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Post-polycythemia Vera Myelofibrosis or Post-PV MF or Myelofib...?
Do you have any of these conditions: Myelosclerosis with myeloid metaplasia or Post-polycythemia Vera Myelofibrosis or Post-PV MF or Myelofibrosis or Post Polycythemia Vera Myelofibrosis ...?
Do you have any of these conditions: Myelofibrosis or Post Polycythemia Vera Myelofibrosis or Post-polycythemia Vera Myelofibrosis or Myelosclerosis with myeloid metaplasia or Post Essent...?
Gender: Male or Female
Age 18 years
Confirmed diagnosis of PMF in accordance with the World Health Organization (WHO) 2016 criteria, or Post-PV/ET MF in accordance with the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT criteria)
Symptomatic, defined as a TSS of 10 units assessed by a single MFSAF v4.0 assessment during Screening prior to Day BL1
Anemic, defined as a Hgb < 10 g/dL in Screening/Baseline period
Previously treated with an approved JAK inhibitor for PMF or Post-PV/ET MF for 90 days, or 28 days if JAK inhibitor therapy is complicated by RBC transfusion requirement of 4 units in 8 weeks, or Grade 3/4 AEs of thrombocytopenia, anemia, or hematoma
Baseline splenomegaly, defined as having a palpable spleen at 5 cm, below the left costal margin, or with volume 450 cm on imaging (ultrasound, MRI or CT are acceptable), assessed during Screening at any point prior to Randomization
High risk, intermediate-2, or intermediate-1 risk MF as defined by DIPSS, or DIPSS-plus
No allogeneic stem cell transplant planned
Acceptable laboratory assessments
Absolute neutrophil count (ANC) 0.75 10/L
Platelet count (PLT) 25 10/L (without requirement for platelet transfusion)
Peripheral blast count < 10%
Alanine aminotransferase/ glutamic-oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/ serum glutamic-pyruvic transaminase (ALT/SGPT) 3 ULN ( 5 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 (CCr) 30 mL/min according to Cockcroft-Gault
Direct bilirubin 2.0 ULN

Exclusion Criteria

Use of the following treatments within the time periods noted
Prior momelotinib treatment at any time
Approved JAK inhibitor therapy (eg, fedratinib or ruxolitinib) within 1 week prior to the first day of Baseline
Active anti-MF therapy within 1 week prior to the first day of Baseline
Potent Cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to Randomization
Investigational agent (including investigational JAK inhibitors) within 4 weeks prior to Randomization
Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization
Danazol within 3 months prior to Randomization
Splenic irradiation within 3 months prior to Randomization
Current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin
History of prostate cancer, with the exception of localized prostate cancer that has been treated surgically or by radiotherapy with curative intent and presumed cured
Prostate specific antigen (PSA) > 4 ng/mL
Unsuitable for spleen volume measurements due to prior splenectomy or unwilling or unable to undergo an MRI or CT scan for spleen volume measurement per protocol requirements
Any of the following (criteria a - k)
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 trial)
Significant active or chronic bleeding event Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization
Unstable angina pectoris within 6 months prior to Randomization
Symptomatic congestive heart failure within 6 months prior to Randomization
Uncontrolled cardiac arrhythmia within 6 months prior to Randomization
QTcF interval > 500 msec, unless attributed to bundle branch block
Current progressive thrombosis despite treatment
History of porphyria
Child-Pugh score 10
Psychiatric illness, social situation, or any other condition that would limit compliance with trial requirements or may interfere with the interpretation of study results, as judged by investigator or sponsor
Inability or unwillingness to comply with the protocol restrictions on MF therapy and other medications prior to and during study treatment
Subjects with a prior or concurrent malignancy, whose natural history or treatment has a significant potential to interfere with the safety or efcacy assessment of the investigational regimen
Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding or thalassemia
Known positive status for HIV
Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier (testing required for hepatitis B and C)
Unresolved non-hematologic toxicities from prior therapies that are > Grade 1 per CTCAE v5.0
Presence of peripheral neuropathy Grade 2 per CTCAE v5.0
Women who are already pregnant or lactating
Additional inclusion/exclusion criteria may apply
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