MyelofibrosisPhase 1/2NCT05280509
Study of TL-895 Combined With Ruxolitinib in JAKi Treatment-Naïve MF Subjects and Subjects With MF Who Have a Suboptimal Response to Ruxolitinib
A Phase 1/2 study testing TL-895 and Ruxolitinib in people with Myelofibrosis and Primary Myelofibrosis, run by Telios Pharma, Inc. at 19 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelofibrosis, Primary Myelofibrosis, Post-PV MF
- What is being tested?
- TL-895 and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 19 sitesin 6 countries
- Study dates
- 9 Jun 2022to Apr 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
19 sites in 6 countries. Contact the study team or a site near you to ask about taking part.
Nikki Stuart contact
19 sites in 6 countries
France5 sites, 5 recruiting
- Recruiting
CHU Angers
Angers, 49100
- Recruiting
AP-HM - Hôpital de la Timone
Marseille, 13005
- Recruiting
CHU de Nice - Hopital L'Archet II
Nice, 06200
- Recruiting
Hôpital Saint Louis - AP-HP
Paris, 75010
- Recruiting
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
United States4 sites, 4 recruiting
- Recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35294
- Recruiting
Gabrail Cancer Center
Canton, Ohio, 44718
- Recruiting
University of Cincinnati (UC)
Cincinnati, Ohio, 45267
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Spain4 sites, 4 recruiting
- Recruiting
Hospital Universitari Arnau de Vilanova
Lleida, 25198
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28034
- Recruiting
Hospital Universitario Virgen de la Victoria
Málaga, 29010
- Recruiting
Hospital Quironsalud de Zaragoza
Zaragoza, 50006
Italy3 sites, 3 recruiting
- Recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola
Bologna, 40138
- Recruiting
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
Milan, 20122
- Recruiting
Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia
Perugia, 06129
Germany2 sites, 2 recruiting
- Recruiting
Marien Hospital Duesseldorf
Düsseldorf, 40479
- Recruiting
Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall
Halle, 40479
Poland1 site, 1 recruiting
- Recruiting
Pratia Onkologia Katowice
Katowice, 40-519
About this study
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
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.
- Being tested
- TL-895, Ruxolitinib
- Keywords
- Myelofibrosis
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TL-895Drug
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
RuxolitinibDrug
Also called Jakafi, Jakavi
Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b - Dose Level 1 | Experimental | 150 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib. Receives: Drug: TL-895; Drug: Ruxolitinib |
| Phase 1b - Dose Level 2 | Experimental | 300 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib. Receives: Drug: TL-895; Drug: Ruxolitinib |
| Phase 1b - Dose Level 3 | Experimental | 450 mg of TL-895 will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle combined with the subject's pre-study stable dose of ruxolitinib. Receives: Drug: TL-895; Drug: Ruxolitinib |
| Phase 2 - Cohort 1 JAKi treatment-naïve MF | Experimental | The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
The dose of ruxolitinib will be based on the subject's baseline platelet count. Receives: Drug: TL-895; Drug: Ruxolitinib |
| Phase 2 - Cohort 2 suboptimal response to Ruxolitinib | Experimental | The RP2D of TL-895 as determined in Phase 1b will be administered orally, twice daily (BID) continuously starting on Day 1 in a 28-day cycle.
The dose schedule will be the stable ruxolitinib dose schedule as the subject is currently taking prior to entry into the study. Receives: Drug: TL-895; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib
Dose-limiting toxicities (DLTs) will be used to establish the maximum-tolerated dose (MTD) of TL-895 in combination with ruxolitinib. The safety review committee (SRC) will determine the RP2D based on safety and efficacy data of the combination of TL-895 and ruxolitinib.
Measured: 28 days
Phase 2 - Spleen Volume Reduction (SVR) at Week 24
The proportion of subjects achieving SVR of ≥35% at Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
Measured: 24 Weeks
Secondary outcomes (6)
Phase 1b - Spleen Volume Reduction (SVR) at Week 24
The proportion of subjects achieving ≥35% SVR at Week 24 by MRI or CT scan.
Measured: 24 Weeks
Phase 1b - TSS reduction at Week 24
The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0.
Measured: 24 Weeks
Phase 2 - TSS reduction at Week 24
The proportion of subjects achieving ≥50% reduction in TSS at Week 24 by MFSAF v4.0.
Measured: 24 Weeks
DOR Spleen
Time from initial SVR of ≥ 35% by MRI/CT until the first occurrence of disease progression or death
Measured: 48 Months
Progression Free Survival
Time from first dose to progression or death from any cause.
Measured: 48 Month
Overall Survival
Time from first dose to death from any cause
Measured: 48 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2022
- Study start9 Jun 2022
- Primary completionOct 2025 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1b - Dose Escalation Design Phase 2 - Dose Expansion
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Telios Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05280509
- Sponsor's protocol ID
- TL-895-209
- Status last verified
- Feb 2023
- First submitted
- 5 Mar 2022
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No