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Relapsed/Refractory B Cell MalignanciesPhase 1/2NCT02825836

Phase I/II, FIH, Dose Escalation Trial of TL-895 and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Tx-Naïve and R/R CLL/SLL Subjects

A Phase 1/2 study testing TL-895 and Navtemadlin in people with Relapsed/Refractory B Cell Malignancies and Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma, run by Telios Pharma, Inc. at 17 sites in 7 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this research study is to determine the safety and tolerability of TL-895. There are 2 parts of this study. Part 1 tested increasing doses of TL-895 to identify the recommended safe dose for participants with relapsed/refractory (R/R) B cell malignancies who failed at least 1 but no more than 3 prior… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
TL-895 and Navtemadlin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
130 participants
Where
17 sitesin 7 countries
Study dates
26 Aug 2016to 1 Dec 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Relapsed/refractory CLL or relapsed/refractory SLL (Arms 1, 2, 5, and 7)
  • Treatment naïve CLL or SLL (Arm 3, 4, and 6)
  • ECOG performance status of ≤ 2
  • Adequate hematologic, hepatic, and renal functions

Who cannot join

  • Prior treatment with any BTK or PI3K inhibitors
  • History of major organ transplant
  • Women who are pregnant or breastfeeding

Trial locations and contacts

17 sites in 7 countries.

17 sites in 7 countries

Poland5 sites

  • Pratia MCM Krakow

    Krakow, 30-510

  • Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny

    Lublin, 20-090

  • Szpital Wojewódzki

    Opole, 46-020

  • Examen sp. z o. o.

    Skorzewo, Poznań, 60-185

  • Nasz Lekarz Przychodnie Medyczne

    Torun, 87-100

Other trials in Poland

Ukraine3 sites

  • Communal Non-profit Enterprise Regional Center of Oncology

    Kharkiv, 61000

  • Kyiv City Clinical Hospital #4

    Kyiv, 03110

  • Mykolaiv Regional Clinical Hospital

    Mykolaiv, 54058

Other trials in Ukraine

United States2 sites

  • Ohio State University Wexner Medical Center

    Columbus, Ohio, 43210

  • The West Clinic

    Germantown, Tennessee, 38138

Other trials in United States

Hungary2 sites

  • Debreceni Egyetem - Borgyógyászati Klinika

    Debrecen, 4002

  • Eger Markhot Ferenc Kórház

    Eger, 3300

Other trials in Hungary

Russia2 sites

  • Saint Petersburg State Medical University

    Saint Petersburg, 197022

  • Yaroslavl Regional Clinical Hospital

    Yaroslavl, 150023

Other trials in Russia

United Kingdom2 sites

  • University College London Hospitals - NIHR/Wellcome Trust

    London

  • Derriford Hospital - Dept of Haematology

    Plymouth

Other trials in United Kingdom

Italy1 site

  • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica

    Bologna, 40138

Other trials in Italy

About this study

Official title: Phase I/II, First in Human, Dose Escalation Trial of TL 895 Monotherapy in Subjects With Relapsed/Refractory B Cell Malignancies and Expansion of TL-895 Monotherapy and Combination Therapy With Navtemadlin in Treatment-Naïve Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Subjects and Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia or Relapsed/Refractory Small Lymphocytic Lymphoma

The purpose of this research study is to determine the safety and tolerability of TL-895. There are 2 parts of this study. Part 1 tested increasing doses of TL-895 to identify the recommended safe dose for participants with relapsed/refractory (R/R) B cell malignancies who failed at least 1 but no more than 3 prior therapies. Part 1 of this study is no longer enrolling participants.

Arms 1 \& 2 of Part 2 of this study will test different doses of TL-895 in participants with R/R CLL or SLL who have failed at least 1 prior therapy. Arms 1 \& 2 of Part 2 of this study is randomized (like the flip of a coin) to receive a specific treatment dose. If someone participates in arms 1 or 2 of Part 2, the dose they receive will be either 100mg twice a day or 150mg twice a day.

Read more

Arms 3 and 4 of Part 2 of this study will test the 150mg and 100mg BID dose of TL-895, respectively in treatment naïve participants with CLL/SLL.

Arms 5 and 6 of Part 2 will test 150mg TL-895 BID in combination with 240 mg navtemadlin QD in participants with relapsed/refractory and treatment naïve without 17p(del). Arm 7 will test 150mg TL-895 in combination with 240 mg navtemadlin QD in participants with relapsed/refractory CLL/SLL with 17p(del).

Every participant in this study will receive TL-895.

Being tested
TL-895, Navtemadlin
Keywords
TL-895, Tyrosine Kinase Inhibitor, Lymphoma, Open, Phase I, Phase II, CLL, SLL
Medical subject headings
Recurrence, Lymphoma, Mantle-Cell, Lymphoma, Large B-Cell, Diffuse, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma

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.

  • NavtemadlinDrug

    Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Study groups in NCT02825836
Study groupRoleWhat they receive
TL-895 80/160 mg QD in R/R ParticipantsExperimentalParticipants received TL-895 80 mg powder in capsule (PiC) orally once daily (OD) for 3 days followed by TL-895 160 mg OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 300 mg QD in R/R ParticipantsExperimentalParticipants received TL-895 300 mg PiC orally OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 600 mg QD in R/R ParticipantsExperimentalParticipants received TL-895 600 mg PiC orally OD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 300 mg BID in R/R ParticipantsExperimentalParticipants received TL-895 300 mg PiC orally twice daily (BID) in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 900 mg QD in R/R ParticipantsExperimentalParticipants received TL-895 900 mg PiC orally QD in fasted state for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 100 mg BID in R/R ParticipantsExperimentalParticipants received TL-895 100 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 150 mg BID in R/R ParticipantsExperimentalParticipants received TL-895 150 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 150 mg BID in Treatment Naïve ParticipantsExperimentalParticipants received TL-895 150 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 100 mg BID in Treatment Naïve ParticipantsExperimentalParticipants received TL-895 100 mg BID orally with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895
TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del)ExperimentalParticipants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895; Drug: Navtemadlin
TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del)ExperimentalParticipants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895; Drug: Navtemadlin
TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del)ExperimentalParticipants received navtemadlin 240 mg administered QD on Days 1-7 in combination with TL-895 150 mg BID orally with food for 28 days with in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.
Receives: Drug: TL-895; Drug: Navtemadlin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1

    DLT is defined as any of the adverse event (AEs) of a certain grade or above, related to drug.

    Measured: Baseline up to the end of cycle 1 (28 days)

  2. Part 2 (Dose Expansion): Overall Response Rate (ORR)

    The proportion of subjects achieving CR, CRi, nodular partial response (nPR), partial response (PR), or PR with lymphocytosis (PR-L) at any time while on the study based on iwCLL response criteria (2), as assessed by investigators

    Measured: Baseline up to end of study (2 years after last patient enrolled)

Secondary outcomes (5)

  1. Part 1 (Dose Escalation): Best Overall Response (BOR)/Progression Free Survival (PFS)

    Defined by the length of time during the treatment of the disease, that a participant lives with the disease but it does not get worse based on investigator assessments

    Measured: Baseline up to 6 months on treatment

  2. Part 2 (Dose Expansion): Overall CR/CRi rate

    The proportion of subjects achieving CR/CRi based on iwCLL response criteria

    Measured: Baseline up to end of study (2 years after last patient enrolled)

  3. Part 2: Duration of Clinical Response (DOR)

    Time from initial response to disease progression or death from any cause

    Measured: Baseline up to end of study (2 years after last patient enrolled)

  4. Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

    Incidence, nature, severity of treatment-emergent adverse events (TEAEs), and deaths, including cause of death, from screening up to the end of study visit of participants with CLL/SLL who have failed at least 1 line of therapy

    Measured: Baseline up to end of study (2 years after last patient enrolled)

  5. Part 2: Assessment of Safety and Tolerability via Clinical Measurements

    Assessments including but not limited to clinical laboratory measurements, ECGs, vital signs, and ECOG performance

    Measured: Baseline up to end of study (2 years after last patient enrolled)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jul 2016 (estimated)
  2. Study start26 Aug 2016
  3. Primary completion1 Dec 2024 (estimated)
  4. Study completion1 Dec 2025 (estimated)

Resources

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
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
130 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02825836
Sponsor's protocol ID
MS200662_0001
Other IDs
2016-000286-23, 2016
Status last verified
Jul 2023
First submitted
1 Jun 2016
Last updated
13 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Eugenio Gaudio, Chiara Tarantelli, Emanuele Zucca, Davide Rossi, Anastasios Stathis, Francesco Bertoni. The two novel BTK-inhibitors M2951 and M7583 show in vivo anti-tumor activity in pre-clinical models of B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4182. doi:10.1158/1538-7445.AM2017-4182

  • Goodstal SM, Lin J, Crandall T, Crowley L, Bender AT, Pereira A, Soloviev M, Wesolowski JS, Iadevaia R, Schelhorn SE, Ross E, Morandi F, Ma J, Clark A. Preclinical evidence for the effective use of TL-895, a highly selective and potent second-generation BTK inhibitor, for the treatment of B-cell malignancies. Sci Rep. 2023 Nov 21;13(1):20412. doi: 10.1038/s41598-023-47735-z.

    PubMed 37989777

  • Jurczak W, Rule S, Townsend W, Tucker D, Sarholz B, Scheele J, Dyroff M, Gribben JG, Dlugosz-Danecka M, Zinzani PL. Phase I, first-in-human trial of Bruton's tyrosine kinase inhibitor M7583 in patients with B-cell malignancies. Leuk Lymphoma. 2021 Oct;62(10):2392-2399. doi: 10.1080/10428194.2021.1913139. Epub 2021 Apr 24.

    PubMed 33896333

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TL-895 and Navtemadlin in people with Relapsed/Refractory B Cell Malignancies and Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma, run by Telios Pharma, Inc. at 17 sites in 7 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 4 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 13 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Poland, Ukraine, United States, Hungary, Russia and 2 more countries. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1 (time frame: Baseline up to the end of cycle 1 (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?

On the ClinicalTrials.gov record for NCT02825836, which also lists 3 linked publications.

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 13 Jul 2023.

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