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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

Primary Purpose

Relapsed/Refractory B Cell Malignancies, Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TL-895
Navtemadlin
Sponsored by
Telios Pharma, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed/Refractory B Cell Malignancies focused on measuring TL-895, Tyrosine Kinase Inhibitor, Lymphoma, Open, Phase I, Phase II, CLL, SLL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

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

Exclusion Criteria

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

Sites / Locations

  • Ohio State University Wexner Medical Center
  • The West Clinic
  • Debreceni Egyetem - Borgyógyászati Klinika
  • Eger Markhot Ferenc Kórház
  • Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica
  • Examen sp. z o. o.
  • Pratia MCM Krakow
  • Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny
  • Szpital Wojewódzki
  • Nasz Lekarz Przychodnie Medyczne
  • Saint Petersburg State Medical University
  • Yaroslavl Regional Clinical Hospital
  • Communal Non-profit Enterprise Regional Center of Oncology
  • Kyiv City Clinical Hospital #4
  • Mykolaiv Regional Clinical Hospital
  • University College London Hospitals - NIHR/Wellcome Trust
  • Derriford Hospital - Dept of Haematology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

TL-895 80/160 mg QD in R/R Participants

TL-895 300 mg QD in R/R Participants

TL-895 600 mg QD in R/R Participants

TL-895 300 mg BID in R/R Participants

TL-895 900 mg QD in R/R Participants

TL-895 100 mg BID in R/R Participants

TL-895 150 mg BID in R/R Participants

TL-895 150 mg BID in Treatment Naïve Participants

TL-895 100 mg BID in Treatment Naïve Participants

TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del)

TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del)

TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del)

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

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
Part 2 (Dose Expansion): Overall CR/CRi rate
The proportion of subjects achieving CR/CRi based on iwCLL response criteria
Part 2: Duration of Clinical Response (DOR)
Time from initial response to disease progression or death from any cause
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
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

Full Information

First Posted
June 1, 2016
Last Updated
July 11, 2023
Sponsor
Telios Pharma, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02825836
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 26, 2016 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Telios Pharma, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/Refractory B Cell Malignancies, Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Treatment-Naive B Cell Malignancies
Keywords
TL-895, Tyrosine Kinase Inhibitor, Lymphoma, Open, Phase I, Phase II, CLL, SLL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TL-895 80/160 mg QD in R/R Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 300 mg QD in R/R Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 600 mg QD in R/R Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 300 mg BID in R/R Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 900 mg QD in R/R Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 100 mg BID in R/R Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 150 mg BID in R/R Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 150 mg BID in Treatment Naïve Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 100 mg BID in Treatment Naïve Participants
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants without 17p(del)
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 150 mg BID & navtemadlin 240mg QD in Treatment Naïve Participants without 17p(del)
Arm Type
Experimental
Arm Description
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.
Arm Title
TL-895 150 mg BID & navtemadlin 240mg QD in R/R Participants with 17p(del)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
TL-895
Intervention Description
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Intervention Type
Drug
Intervention Name(s)
Navtemadlin
Intervention Description
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.
Primary Outcome Measure Information:
Title
Part 1 (Dose Escalation): DLTs (Dose Limiting Toxicities) during Cycle 1
Description
DLT is defined as any of the adverse event (AEs) of a certain grade or above, related to drug.
Time Frame
Baseline up to the end of cycle 1 (28 days)
Title
Part 2 (Dose Expansion): Overall Response Rate (ORR)
Description
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
Time Frame
Baseline up to end of study (2 years after last patient enrolled)
Secondary Outcome Measure Information:
Title
Part 1 (Dose Escalation): Best Overall Response (BOR)/Progression Free Survival (PFS)
Description
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
Time Frame
Baseline up to 6 months on treatment
Title
Part 2 (Dose Expansion): Overall CR/CRi rate
Description
The proportion of subjects achieving CR/CRi based on iwCLL response criteria
Time Frame
Baseline up to end of study (2 years after last patient enrolled)
Title
Part 2: Duration of Clinical Response (DOR)
Description
Time from initial response to disease progression or death from any cause
Time Frame
Baseline up to end of study (2 years after last patient enrolled)
Title
Part 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs)
Description
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
Time Frame
Baseline up to end of study (2 years after last patient enrolled)
Title
Part 2: Assessment of Safety and Tolerability via Clinical Measurements
Description
Assessments including but not limited to clinical laboratory measurements, ECGs, vital signs, and ECOG performance
Time Frame
Baseline up to end of study (2 years after last patient enrolled)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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 Exclusion Criteria Prior treatment with any BTK or PI3K inhibitors History of major organ transplant Women who are pregnant or breastfeeding
Facility Information:
Facility Name
Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
The West Clinic
City
Germantown
State/Province
Tennessee
ZIP/Postal Code
38138
Country
United States
Facility Name
Debreceni Egyetem - Borgyógyászati Klinika
City
Debrecen
ZIP/Postal Code
4002
Country
Hungary
Facility Name
Eger Markhot Ferenc Kórház
City
Eger
ZIP/Postal Code
3300
Country
Hungary
Facility Name
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica
City
Bologna
ZIP/Postal Code
40138
Country
Italy
Facility Name
Examen sp. z o. o.
City
Skorzewo
State/Province
Poznań
ZIP/Postal Code
60-185
Country
Poland
Facility Name
Pratia MCM Krakow
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny
City
Lublin
ZIP/Postal Code
20-090
Country
Poland
Facility Name
Szpital Wojewódzki
City
Opole
ZIP/Postal Code
46-020
Country
Poland
Facility Name
Nasz Lekarz Przychodnie Medyczne
City
Toruń
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Saint Petersburg State Medical University
City
Saint Petersburg
ZIP/Postal Code
197022
Country
Russian Federation
Facility Name
Yaroslavl Regional Clinical Hospital
City
Yaroslavl
ZIP/Postal Code
150023
Country
Russian Federation
Facility Name
Communal Non-profit Enterprise Regional Center of Oncology
City
Kharkiv
ZIP/Postal Code
61000
Country
Ukraine
Facility Name
Kyiv City Clinical Hospital #4
City
Kyiv
ZIP/Postal Code
03110
Country
Ukraine
Facility Name
Mykolaiv Regional Clinical Hospital
City
Mykolaiv
ZIP/Postal Code
54058
Country
Ukraine
Facility Name
University College London Hospitals - NIHR/Wellcome Trust
City
London
Country
United Kingdom
Facility Name
Derriford Hospital - Dept of Haematology
City
Plymouth
Country
United Kingdom

12. IPD Sharing Statement

Citations:
Citation
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
Results Reference
background
Citation
Samantha M. Goodstal, Jianguo Ma, Jing Lin, Timothy Crandall, Lindsey Crowley, Andrew Bender, Riham Iadevaia and Anderson Clark. M7583 Is a Highly Selective and Potent Second Generation BTK Inhibitor for Treatment of B-Cell Malignancies. Blood 2017 130:3845.
Results Reference
background
PubMed Identifier
33896333
Citation
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.
Results Reference
background

Learn more about this trial

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

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