Phase I/II, First in Human, Dose Escalation Trial of TL-895 in Subjects With R/R CLL/SLL and Expansion in Treatment Naïve CLL/SLL Subjects and Subjects With R/R CLL/SLL

Sponsor

Telios Pharma, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02825836

Collaborator

(none)

Enrollment

Locations

Arms

99.2

Anticipated Duration (Months)

4.4

Patients Per Site

Patients Per Site Per Month

Study Details

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. Every participant in this study will receive TL-895.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory B Cell Malignancies Mantle Cell Lymphoma and Diffuse Large B Cell Lymphoma Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma	Drug: TL-895	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I/II, First in Human, Dose Escalation Trial of TL 895 in Subjects With Relapsed/Refractory B Cell Malignancies and Expansion 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

Actual Study Start Date :

Aug 26, 2016

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TL-895 80/160 mg QD in R/R Participants 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.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: TL-895 300 mg QD in R/R Participants 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.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: TL-895 600 mg QD in R/R Participants 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.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: TL-895 300 mg BID in R/R Participants 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.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: TL-895 900 mg QD in R/R Participants 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.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: TL-895 100 mg BID in R/R Participants Participants received TL-895 100 mg BID orally BID with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: TL-895 150 mg BID in R/R Participants Participants received TL-895 150 mg BID orally BID with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: TL-895 150 mg BID in Treatment Naïve Participants Participants received TL-895 150 mg BID orally BID with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
Experimental: TL-895 100 mg BID in Treatment Naïve Participants Participants received TL-895 100 mg BID orally BID with food for 28 days in each 28 day cycle until disease progression, withdrawal of consent, or discontinuation from the study.	Drug: TL-895 TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ohio State University Wexner Medical Center	Columbus	Ohio	United States	43210
2	The West Clinic	Germantown	Tennessee	United States	38138
3	Debreceni Egyetem - Borgyógyászati Klinika	Debrecen		Hungary	4002
4	Eger Markhot Ferenc Kórház	Eger		Hungary	3300
5	Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Istituto di Ematologia e Oncologia Medica	Bologna		Italy	40138
6	Examen sp. z o. o.	Skorzewo	Poznań	Poland	60-185
7	Pratia MCM Krakow	Krakow		Poland	30-510
8	Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli Oddzial Hematologiczny	Lublin		Poland	20-090
9	Szpital Wojewódzki	Opole		Poland	46-020
10	Nasz Lekarz Przychodnie Medyczne	Toruń		Poland	87-100
11	Saint Petersburg State Medical University	Saint Petersburg		Russian Federation	197022
12	Yaroslavl Regional Clinical Hospital	Yaroslavl		Russian Federation	150023
13	Communal Non-profit Enterprise Regional Center of Oncology	Kharkiv		Ukraine	61000
14	Kyiv City Clinical Hospital #4	Kyiv		Ukraine	03110
15	Mykolaiv Regional Clinical Hospital	Mykolaiv		Ukraine	54058
16	Barts Hospital - Cancer Centre	London		United Kingdom
17	University College London Hospitals - NIHR/Wellcome Trust	London		United Kingdom
18	Derriford Hospital - Dept of Haematology	Plymouth		United Kingdom