Clinical trial NCT04655118: Study of TL-895 in Subjects With Myelofibrosis or Indolent Systemic Mastocytosis
Official title: A Phase 2 Multicenter Study of TL-895 in Subjects With Relapsed/Refractory Myelofibrosis, Janus Kinase Inhibitor Intolerant Myelofibrosis, Janus Kinase Inhibitor Treatment Ineligible Myelofibrosis, or Indolent Systemic Mastocytosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myelofibrosis
Indolent Systemic Mastocytosis
Lead sponsor: Telios Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2020-12-07
Enrollment: 121
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 evaluates TL-895, a potent, orally-available and highly selective irreversible tyrosine kinase inhibitor for the treatment of Myelofibrosis (Cohorts 1-3) or Indolent Systemic Mastocytosis (Cohort 5). Participants must be diagnosed with Myelofibrosis and be relapsed/refractory (e.g., having failed prior therapy), intolerant, or ineligible to receive JAKi treatment, or be diagnosed with Indolent Systemic Mastocytosis.


Eligibility criteria: Cohorts 1-3

Key Inclusion Criteria:

* Adults ≥18 years of age
* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
* Adequate hematologic, hepatic, and renal functions
* MF symptoms as defined by having at least 2 symptoms with an average baseline (Day -7 to Day -1) score of at least 1 for each of the 2 symptoms per MFSAF v4.0
* Cohort 3 only: Ineligibility for JAKi treatment with a platelet count of ≥ 25 and \< 50 x 10\^9/L

Key Exclusion Criteria:

* Prior treatment with any BTK or BMX inhibitors
* Prior treatment with JAKi within 28 days prior to study treatment
* Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment

Cohort 5

Key Inclusion Criteria:

* Adults ≥18 years of age
* Confirmed diagnosis of ISM as defined by WHO diagnostic criteria based on review of bone marrow biopsy pathology report results
* Subject must have moderate-to-severe symptoms

Key Exclusion Criteria:

* Prior treatment with any BTK or BMX inhibitors
* Prior treatment with Avapritinib, bezuclastinib, or BLU-263/elenestinib
* Diagnosis with another myeloproliferative disorder

Primary outcomes:
measure: Cohorts 1-3: Determine the RP2D of TL-895
timeFrame: 9 months
measure: Cohort 5: Determine the RP2D of TL-895
timeFrame: Week 24
Secondary outcomes:
measure: Cohorts 1-3: Spleen volume reduction (SVR) rate
timeFrame: Week 24
measure: Cohort 5: Changes in patient reported symptoms
timeFrame: Week 12
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado - Aurora Cancer Center
state: Colorado
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati (UC) Physicians Company, LLC
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: East Albury
country: Australia
facility: Border Medical Oncology
city: Kogarah
country: Australia
facility: Southern Oncology Specialists
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Sydney
country: Australia
facility: St Vincent's Hospital Sydney
city: Liège
country: Belgium
facility: Chu De Liège
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: São Paulo
country: Brazil
facility: Instituto de Estudos e Pesquisas Sao Lucas - IEP - Sao Lucas
city: Sofia
country: Bulgaria
facility: University Hospital "St Ivan Rilski"
city: Sofia
country: Bulgaria
facility: Military Medical Academy
city: Le Mans
country: France
facility: CH Le Mans
city: Nantes
country: France
facility: CHU de Nantes - Hôtel-Dieu
city: Nice
country: France
facility: CHU de Nice - Hopital L' Archet II
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden
city: Düsseldorf
country: Germany
facility: Marien Hospital Duesseldorf
city: Halle
country: Germany
facility: Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall
city: Jena
country: Germany
facility: Universitaetsklinikum Jena
city: Koblenz
country: Germany
facility: Praxisklinik fur Hamatologie und Onkologie
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz es Rendelointezet
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmár-Bereg Megyei Önkormányzat Jósa András Oktatókórház Megyei-Városi Tüdőgondozó Intézete
city: Székesfehérvár
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico G. Rodolico-San Marco - Presidio Ospedaliero G. Rodolico
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore Della Carita'
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia
city: Ravenna
country: Italy
facility: AUSL della Romagna-Ospedale S.Maria delle Croci
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano Bianchi Melacrino Morelli
city: Roma
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Umberto I
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital, The Catholic University of Korea
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki Nr 2 im. Dr Jana Biziela w Bydgoszczy, Klinika Hematologi
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Hematologii i Transplantologii
city: Kraków
country: Poland
facility: Klinika Hematologii Collegium Medicum Uniwersytetu Jagiellonskiego
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu, Klinika Hematologii, Nowotworów Krwi i Transplantacji Szpiku
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia - L'Hospitalet
city: Barcelona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Salamanca University Hospital
city: Zaragoza
country: Spain
facility: Hospital Quirónsalud Zaragoza
city: Kaohsiung City
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung Branch
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References: