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
- Conditions
- Relapsed/Refractory B Cell MalignanciesMantle Cell Lymphoma and Diffuse Large B Cell LymphomaChronic Lymphocytic LeukemiaSmall Lymphocytic LymphomaTreatment-Naive B Cell Malignancies
- Interventions
- Registration Number
- NCT02825836
- Lead Sponsor
- Telios Pharma, Inc.
- Brief 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 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.
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 130
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description TL-895 300 mg BID in R/R Participants TL-895 Participants 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. TL-895 900 mg QD in R/R Participants TL-895 Participants 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. TL-895 80/160 mg QD in R/R Participants TL-895 Participants 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. TL-895 300 mg QD in R/R Participants TL-895 Participants 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. TL-895 600 mg QD in R/R Participants TL-895 Participants 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. TL-895 100 mg BID in Treatment Naïve Participants TL-895 Participants 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. TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del) Navtemadlin Participants 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. TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del) Navtemadlin Participants 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. TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del) TL-895 Participants 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. TL-895 100 mg BID in R/R Participants TL-895 Participants 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. TL-895 150 mg BID in R/R Participants TL-895 Participants 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. TL-895 150 mg BID in Treatment Naïve Participants TL-895 Participants 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. TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del) TL-895 Participants 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. TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del) TL-895 Participants 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. TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del) Navtemadlin Participants 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.
- Primary Outcome Measures
Name Time Method Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1 Baseline up to the end of cycle 1 (28 days) DLT is defined as any of the adverse event (AEs) of a certain grade or above, related to drug.
Part 2 (Dose Expansion): Overall Response Rate (ORR) Baseline up to end of study (2 years after last patient enrolled) 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
- Secondary Outcome Measures
Name Time Method Part 1 (Dose Escalation): Best Overall Response (BOR)/Progression Free Survival (PFS) Baseline up to 6 months on treatment 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
Part 2 (Dose Expansion): Overall CR/CRi rate Baseline up to end of study (2 years after last patient enrolled) The proportion of subjects achieving CR/CRi based on iwCLL response criteria
Part 2: Duration of Clinical Response (DOR) Baseline up to end of study (2 years after last patient enrolled) Time from initial response to disease progression or death from any cause
Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Baseline up to end of study (2 years after last patient enrolled) 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
Part 2: Assessment of Safety and Tolerability via Clinical Measurements Baseline up to end of study (2 years after last patient enrolled) Assessments including but not limited to clinical laboratory measurements, ECGs, vital signs, and ECOG performance
Trial Locations
- Locations (17)
Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
Pratia MCM Krakow
🇵🇱Krakow, Poland
Szpital Wojewódzki
🇵🇱Opole, Poland
Mykolaiv Regional Clinical Hospital
🇺🇦Mykolaiv, Ukraine
University College London Hospitals - NIHR/Wellcome Trust
🇬🇧London, United Kingdom
Derriford Hospital - Dept of Haematology
🇬🇧Plymouth, United Kingdom
The West Clinic
🇺🇸Germantown, Tennessee, United States
Debreceni Egyetem - Borgyógyászati Klinika
🇭🇺Debrecen, Hungary
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica
🇮🇹Bologna, Italy
Examen sp. z o. o.
🇵🇱Skorzewo, Poznań, Poland
Saint Petersburg State Medical University
🇷🇺Saint Petersburg, Russian Federation
Yaroslavl Regional Clinical Hospital
🇷🇺Yaroslavl, Russian Federation
Communal Non-profit Enterprise Regional Center of Oncology
🇺🇦Kharkiv, Ukraine
Kyiv City Clinical Hospital #4
🇺🇦Kyiv, Ukraine
Eger Markhot Ferenc Kórház
🇭🇺Eger, Hungary
Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny
🇵🇱Lublin, Poland
Nasz Lekarz Przychodnie Medyczne
🇵🇱Toruń, Poland