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
- Are there results?
- Not yet: the study is under way
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
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05280509
- Acronym / sponsor ID
- TL-895-209
- Keywords
- Myelofibrosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Telios Pharma, Inc.Industry (pharma, biotech, devices)
- Study start
- 9 Jun 2022 (actual)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 15 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Phase 1b - Dose Escalation Design Phase 2 - Dose Expansion
| Arm | Type | Receives |
|---|---|---|
| Phase 1b - Dose Level 1 | Experimental | Drug: TL-895, Drug: Ruxolitinib150 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. |
| Phase 1b - Dose Level 2 | Experimental | Drug: TL-895, Drug: Ruxolitinib300 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. |
| Phase 1b - Dose Level 3 | Experimental | Drug: TL-895, Drug: Ruxolitinib450 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. |
| Phase 2 - Cohort 1 JAKi treatment-naïve MF | Experimental | Drug: TL-895, Drug: RuxolitinibThe 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. |
| Phase 2 - Cohort 2 suboptimal response to Ruxolitinib | Experimental | Drug: TL-895, Drug: RuxolitinibThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (7 listed)
- Prior treatment with any JAKi
- Documented disease progression while on ruxolitinib treatment
- Prior splenectomy or splenic irradiation within 24 weeks prior to first dose of study treatment
- Prior treatment with a BTK or BMX inhibitor
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TL-895TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth. | Drug | Phase 1b - Dose Level 1, Phase 1b - Dose Level 2, Phase 1b - Dose Level 3, Phase 2 - Cohort 1 JAKi treatment-naïve MF, Phase 2 - Cohort 2 suboptimal response to Ruxolitinib |
| RuxolitinibAlso: Jakafi, JakaviRuxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth. | Drug | Phase 1b - Dose Level 1, Phase 1b - Dose Level 2, Phase 1b - Dose Level 3, Phase 2 - Cohort 1 JAKi treatment-naïve MF, Phase 2 - Cohort 2 suboptimal response to Ruxolitinib |
Primary outcome
Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib
Time frame: 28 days
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.
Phase 2 - Spleen Volume Reduction (SVR) at Week 24
Time frame: 24 Weeks
The proportion of subjects achieving SVR of ≥35% at Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) scan.
6 secondary outcomes
Phase 1b - Spleen Volume Reduction (SVR) at Week 24
Time frame: 24 Weeks
Phase 1b - TSS reduction at Week 24
Time frame: 24 Weeks
Phase 2 - TSS reduction at Week 24
Time frame: 24 Weeks
DOR Spleen
Time frame: 48 Months
Progression Free Survival
Time frame: 48 Month
Overall Survival
Time frame: 48 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
Related trials for Myelofibrosis
RecruitingPhase 3
A Phase 3 Study of Pelabresib (DAK539) and Ruxolitinib in Myelofibrosis (MF)
Primary Myelofibrosis (PMF), Post-polycythemia Vera Myelofibrosis (PPV-MF)
RecruitingPhase 3
A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib
Myelofibrosis, Anemia
RecruitingObservational study
Motor Development and Early Predictors of Psychomotor Outcomes in Preterm and Term Infants Assessed by MOS-R and Caregiver Questionnaire at 18 and 36 Months
Neurodevelopmental Disorders, Motor Skills Disorders
Active, not recruitingPhase 3
Study of Selinexor in Combination With Ruxolitinib in Myelofibrosis
Myelofibrosis
RecruitingPhase 2
Study of Momelotinib in Combination With Luspatercept in Participants With Transfusion Dependent Myelofibrosis
Primary Myelofibrosis, Myelofibrosis; Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Nikki Stuart contact
19 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in France, United States, Spain, Italy, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact John Mei (650-542-0136, jmei@teliospharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1b - Recommended Phase 2 dose of TL-895 in combination with ruxolitinib (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.