Clinical trial NCT05280509: Study of TL-895 Combined With Ruxolitinib in JAKi Treatment-Naïve MF Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib
Official title: An Open-Label, Multicenter, Phase 1b/2 Study of the Safety and Efficacy of TL-895 Combined With Ruxolitinib in Janus-associated Kinase Inhibitor (JAKi) Treatment-Naïve Myelofibrosis (MF) Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Myelofibrosis
Primary Myelofibrosis
Post-PV MF
Post-ET Myelofibrosis
Keywords: Myelofibrosis
Lead sponsor: Telios Pharma, Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 1b - Dose Escalation Design Phase 2 - Dose Expansion
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. Participants must have MF (PMF, Post PV MF, or Post ET MF) who are JAKi treatment-naïve or those who have a suboptimal response to ruxolitinib.


Eligibility criteria: Inclusion Criteria:

Subjects with suboptimal response to ruxolitinib:

* Treatment with at a stable dose of ruxolitinib prior to study entry
* Subjects ≥ 18 years of age and able to provide informed consent.
* Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by treating physician according to the World Health Organization (WHO) criteria
* High-risk, intermediate-2 risk, or intermediate-1 risk, defined by Dynamic International Prognostic System (DIPSS)
* Palpable spleen measuring ≥ 5 cm below the left lower coastal margin (LLCM) or spleen volume of ≥ 450 cm3 by MRI or CT scan assessment
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
* Adequate hematological, hepatic, \& renal function.

Exclusion Criteria:

Treatment-naive subjects:

* Prior treatment with any JAKi

Subjects with suboptimal response to ruxolitinib:

* Documented disease progression while on ruxolitinib treatment

All subjects:

* Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment
* Prior treatment with a BTK or BMX inhibitor

Primary outcomes:
measure: Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib
timeFrame: 28 days
measure: Phase 2 - Spleen Volume Reduction (SVR) at Week 24
timeFrame: 24 Weeks
Secondary outcomes:
measure: Phase 1b - Spleen Volume Reduction (SVR) at Week 24
timeFrame: 24 Weeks
measure: Phase 1b - TSS reduction at Week 24
timeFrame: 24 Weeks
measure: Phase 2 - TSS reduction at Week 24
timeFrame: 24 Weeks
measure: DOR Spleen
timeFrame: 48 Months
measure: Progression Free Survival
timeFrame: 48 Month
measure: Overall Survival
timeFrame: 48 Months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati (UC)
state: Ohio
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Angers
country: France
facility: CHU Angers
city: Marseille
country: France
facility: AP-HM - Hôpital de la Timone
city: Nice
country: France
facility: CHU de Nice - Hopital L'Archet II
city: Paris
country: France
facility: Hôpital Saint Louis - AP-HP
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Düsseldorf
country: Germany
facility: Marien Hospital Duesseldorf
city: Halle
country: Germany
facility: Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
city: Perugia
country: Italy
facility: Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Lleida
country: Spain
facility: Hospital Universitari Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Zaragoza
country: Spain
facility: Hospital Quironsalud de Zaragoza
Study officials:
References: