NCT05280509

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.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
70

participants targeted

Target at P75+ for phase_1

Timeline
11mo left

Started Jun 2022

Longer than P75 for phase_1

Geographic Reach
6 countries

19 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress81%
Jun 2022Apr 2027

First Submitted

Initial submission to the registry

March 5, 2022

Completed
10 days until next milestone

First Posted

Study publicly available on registry

March 15, 2022

Completed
3 months until next milestone

Study Start

First participant enrolled

June 9, 2022

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2025

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2027

Expected
Last Updated

February 21, 2023

Status Verified

February 1, 2023

Enrollment Period

3.3 years

First QC Date

March 5, 2022

Last Update Submit

February 16, 2023

Conditions

MyelofibrosisPrimary MyelofibrosisPost-PV MFPost-ET Myelofibrosis

Keywords

Myelofibrosis

Outcome Measures

Primary Outcomes (2)

  • 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.

    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.

    24 Weeks

Secondary Outcomes (6)

  • Phase 1b - Spleen Volume Reduction (SVR) at Week 24

    24 Weeks

  • Phase 1b - TSS reduction at Week 24

    24 Weeks

  • Phase 2 - TSS reduction at Week 24

    24 Weeks

  • DOR Spleen

    48 Months

  • Progression Free Survival

    48 Month

  • +1 more secondary outcomes

Study Arms (5)

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.

Drug: TL-895Drug: 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.

Drug: TL-895Drug: 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.

Drug: TL-895Drug: 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.

Drug: TL-895Drug: 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.

Drug: TL-895Drug: Ruxolitinib

Interventions

TL-895DRUG

TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

Phase 1b - Dose Level 1Phase 1b - Dose Level 2Phase 1b - Dose Level 3Phase 2 - Cohort 1 JAKi treatment-naïve MFPhase 2 - Cohort 2 suboptimal response to Ruxolitinib
RuxolitinibDRUG

Ruxolitinib is an FDA-approved janus kinase inhibitor anticancer drug taken by mouth.

Also known as: Jakafi, Jakavi
Phase 1b - Dose Level 1Phase 1b - Dose Level 2Phase 1b - Dose Level 3Phase 2 - Cohort 1 JAKi treatment-naïve MFPhase 2 - Cohort 2 suboptimal response to Ruxolitinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

Gabrail Cancer Center

Canton, Ohio, 44718, United States

RECRUITING

University of Cincinnati (UC)

Cincinnati, Ohio, 45267, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

CHU Angers

Angers, 49100, France

RECRUITING

AP-HM - Hôpital de la Timone

Marseille, 13005, France

RECRUITING

CHU de Nice - Hopital L'Archet II

Nice, 06200, France

RECRUITING

Hôpital Saint Louis - AP-HP

Paris, 75010, France

RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

RECRUITING

Marien Hospital Duesseldorf

Düsseldorf, 40479, Germany

RECRUITING

Klinik fur Innere Medizin IV - Hamatologie/Onkologie, Universitatsklinikum Hall

Halle, 40479, Germany

RECRUITING

IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola

Bologna, 40138, Italy

RECRUITING

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, 20122, Italy

RECRUITING

Azienda Ospedaliera di Perugia-Ospedale S. Maria della Misericordia

Perugia, 06129, Italy

RECRUITING

Pratia Onkologia Katowice

Katowice, 40-519, Poland

RECRUITING

Hospital Universitari Arnau de Vilanova

Lleida, 25198, Spain

RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Hospital Quironsalud de Zaragoza

Zaragoza, 50006, Spain

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Central Study Contacts

John Mei

CONTACT

650-542-0136jmei@teliospharma.com

Nikki Stuart

CONTACT

nzona@teliospharma.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Phase 1b - Dose Escalation Design Phase 2 - Dose Expansion
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 5, 2022

First Posted

March 15, 2022

Study Start

June 9, 2022

Primary Completion

October 1, 2025

Study Completion (Estimated)

April 1, 2027

Last Updated

February 21, 2023

Record last verified: 2023-02

Locations

IT(3)ES(4)FR(5)PL(1)DE(2)US(4)