JOURNAL ONKOLOGIE – STUDIE
A Study of Momelotinib Versus Danazol in Symptomatic and Anemic Myelofibrosis Patients (MOMENTUM)
Rekrutierend
NCT-Nummer:
NCT04173494
Studienbeginn:
Februar 2020
Letztes Update:
06.04.2021
Wirkstoff:
Momelotinib, Danazol, Placebo to match momelotinib, Placebo to match danazol
Indikation (Clinical Trials):
Polycythemia Vera, Primary Myelofibrosis, Polycythemia, Thrombocytosis, Thrombocythemia, Essential
Geschlecht:
Alle
Altersgruppe:
Erwachsene (18+)
Phase:
Phase 3
Sponsor:
Sierra Oncology, Inc.
Collaborator:
-
Studienleiter
Principal Investigator
Department of Leukemia, The University of Texas MD Anderson Cancer Center
Kontakt
Kontakt:
E-Mail: Sierra_Momentum_ct.gov@clin-edge.com» Kontaktdaten anzeigen
Studienlocations
(3 von 167)
52074 Aachen
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Hufelandstraße 55
45147 Essen
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32429 Minden
(Nordrhein-Westfalen)
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Ernst-Grube-Straße 40
06120 Halle (Saale)
(Sachsen-Anhalt)
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01307 Dresden
(Sachsen)
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4103 Leipzig
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07747 Jena
(Thüringen)
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Kerpener Straße 62
50937 Köln
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23538 Lübeck
(Schleswig-Holstein)
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73557 Mutlangen
(Baden-Württemberg)
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85054 Phoenix
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92614 Irvine
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91011 Los Angeles
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90603 Whittier
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80045 Aurora
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20057 Washington
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33612 Tampa
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60008 Rolling Meadows
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63110 Saint Louis
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07601 Hackensack
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10032 New York
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44011 Avon
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44718 Canton
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44106 Cleveland
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15224 Pittsburgh
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77030 Houston
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78229 San Antonio
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2605 Garran
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2298 Waratah
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5042 Bedford Park
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3004 Melbourne
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6000 Perth
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6020 Innsbruck
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4020 Linz
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1090 Wien
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4400 Steyr
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1070 Bruxelles
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6000 Charleroi
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8000 Brugge
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2060 Antwerpen
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B-4000 Liège
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5800 Pleven
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1431 Sofia
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1756 Sofia
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V6Z 1Y6 Vancouver
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625 00 Brno
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2730 Herlev
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9000 Aalborg
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4000 Roskilde
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5000 Odense
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33604 Pessac
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14033 Caen
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59037 Lille
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75010 Paris
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75571 Paris
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87042 Limoges
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62307 Lens
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72037 Le Mans
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80054 Amiens
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06200 Nice
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69495 Pierre-Bénite
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49 933 Angers
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59000 Lille
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13385 Marseille
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68100 Mulhouse
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44000 Nantes
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86021 Poitiers
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7624 Pécs
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4032 Debrecen
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2800 Tatabánya
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1097 Budapest
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7400 Kaposvár
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4400 Nyíregyháza
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9700 Szombathely
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1083 Budapest
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9023 Győr
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7030000 Be'er Ya'aqov
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31048 Haifa
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Jerusalem
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3109601 Haifa
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3436212 Haifa
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9103102 Jerusalem
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4428164 Kfar Saba
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4941492 Petah tikva
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50134 Firenze
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71013 San Giovanni Rotondo
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47014 Meldola
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61121 Pesaro
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85028 Rionero In Vulture
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10126 Torino
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15121 Alessandria
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40138 Bologna
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16132 Genova
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20122 Milano
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20162 Milano
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80131 Napoli
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28100 Novara
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00161 Roma
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20123 Roma
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33100 Udine
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21100 Varese
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37134 Verona
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41944 Daegu
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47392 Busan
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48108 Busan
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13620 Seongnam-si
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03722 Seoul
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06591 Seoul
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Seoul
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44033 Ulsan
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0622 Auckland
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2025 Auckland
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50-367 Wrocław
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20-081 Lublin
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31-501 Kraków
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02-776 Warszawa
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03-401 Warszawa
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31-826 Kraków
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45-064 Opole
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80-214 Gdańsk
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41-503 Chorzów
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93-513 Łódź
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200143 Craiova
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700483 Iaşi
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540136 Târgu-Mureş
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500366 Braşov
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030 171 Bucharest
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169608 Singapore
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308433 Singapore
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33011 Oviedo
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08003 Barcelona
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08035 Barcelona
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08916 Barcelona
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10003 Cáceres
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17007 Girona
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28034 Madrid
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28041 Madrid
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29010 Málaga
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37007 Salamanca
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41013 Sevilla
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46009 Valencia
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50012 Zaragoza
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171 76 Solna
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413 45 Göteborg
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45153 Uddevalla
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613 Puzi City
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40447 Taichung City
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10002 Taipei
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333 Taoyuan
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PE21 9QS Boston
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BS2 8ED Bristol
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NW1 2PG London
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SE1 9RT London
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W12 0HS London
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SO16 6YD Southampton
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Studien-Informationen
Brief 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.
Ein-/Ausschlusskriterien
Inclusion Criteria:1. Age ≥ 18 years.
2. 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).
3. Symptomatic, defined as a TSS of ≥ 10 units assessed by a single MFSAF v4.0 assessment
during Screening prior to Day BL1.
4. Anemic, defined as a Hgb < 10 g/dL in Screening/Baseline period.
5. 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.
6. Baseline splenomegaly, defined as having a palpable spleen at ≥ 5 cm, below the left
costal margin, or with volume ≥ 450 cm³ on imaging (ultrasound, MRI or CT are
acceptable), assessed during Screening at any point prior to Randomization.
7. High risk, intermediate-2, or intermediate-1 risk MF as defined by DIPSS, or
DIPSS-plus.
8. No allogeneic stem cell transplant planned.
9. Acceptable laboratory assessments:
- Absolute neutrophil count (ANC) ≥ 0.75 × 10⁹/L.
- Platelet count (PLT) ≥ 25 × 10⁹/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:
1. Use of the following treatments within the time periods noted:
1. Prior momelotinib treatment at any time.
2. Approved JAK inhibitor therapy (eg, fedratinib or ruxolitinib) within 1 week
prior to the first day of Baseline.
3. Active anti-MF therapy within 1 week prior to the first day of Baseline.
4. Potent Cytochrome P450 3A4 (CYP3A4) inducers within 1 week prior to
Randomization.
5. Investigational agent (including investigational JAK inhibitors) within 4 weeks
prior to Randomization.
6. Erythropoiesis stimulating agent (ESA) within 4 weeks prior to Randomization.
7. Danazol within 3 months prior to Randomization.
8. Splenic irradiation within 3 months prior to Randomization.
9. Current treatment with simvastatin, atorvastatin, lovastatin or rosuvastatin.
2. 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.
3. Prostate specific antigen (PSA) > 4 ng/mL.
4. 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.
5. Any of the following (criteria a - k):
1. 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).
2. Significant active or chronic bleeding event ≥ Grade 2 per Common Terminology
Criteria for Adverse Events (CTCAE) v5.0, within 4 weeks prior to Randomization.
3. Unstable angina pectoris within 6 months prior to Randomization.
4. Symptomatic congestive heart failure within 6 months prior to Randomization.
5. Uncontrolled cardiac arrhythmia within 6 months prior to Randomization.
6. QTcF interval > 500 msec, unless attributed to bundle branch block.
7. Current progressive thrombosis despite treatment.
8. History of porphyria.
9. Child-Pugh score ≥ 10.
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.
11. Inability or unwillingness to comply with the protocol restrictions on MF therapy
and other medications prior to and during study treatment.
6. Subjects with a prior or concurrent malignancy, whose natural history or treatment has
a significant potential to interfere with the safety or efficacy assessment of the
investigational regimen.
7. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies,
or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding or
thalassemia.
8. Known positive status for HIV.
9. Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C
carrier (testing required for hepatitis B and C).
10. Unresolved non-hematologic toxicities from prior therapies that are > Grade 1 per
CTCAE v5.0.
11. Presence of peripheral neuropathy ≥ Grade 2 per CTCAE v5.0.
12. Women who are already pregnant or lactating.
Additional inclusion/exclusion criteria may apply.
Studien-Rationale
Primary outcome:1. Total Symptom Score (TSS) response rate at Week 24 measured using the Myelofibrosis Symptom Assessment Form v4.0 (Time Frame - Week 24 landmark.):
Difference in TSS response rate at Week 24. TSS response is defined as the proportion of subjects who achieve a ≥ 50% reduction in TSS over the 28 days immediately prior to the end of Week 24 compared to baseline
Secondary outcome:
1. Transfusion independence (TI) status at Week 24 (Time Frame - Week 24 landmark.):
Proportion of subjects with TI status at the end of Week 24. TI is defined as not requiring RBC transfusion (except in the case of clinically overt bleeding) for ≥ 12 weeks immediately prior to the end of Week 24, with Hgb levels ≥ 8 g/dL.
2. Splenic response rate (SRR) at Week 24 (Time Frame - Week 24):
Proportion of subjects who have splenic response (reduction in spleen volume of ≥ 35% from baseline) at the end of Week 24
Studien-Arme
- Experimental: Momelotinib
Participants will receive momelotinib plus placebo to match danazol - Active Comparator: Danazol
Participants will receive danazol plus placebo to match momelotinib
Geprüfte Regime
- Momelotinib (MMB, GS-0387, CYT387):
Momelotinib tablets will be self-administered orally once daily - Danazol (Danocrine):
Danazol capsules will be self-administered orally twice daily - Placebo to match momelotinib:
Momelotinib placebo tablets will be self-administered orally once daily - Placebo to match danazol:
Danazol placebo capsules will be self-administered orally twice daily
Quelle: ClinicalTrials.gov
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