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
Conditions
Keywords
TL-895, Tyrosine Kinase Inhibitor, Lymphoma, Open, Phase I, Phase II, CLL, SLL
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.
Interventions
DRUGTL-895
TL-895 is an experimental tyrosine kinase inhibitor anticancer drug taken by mouth.
DRUGNavtemadlin
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.
Sponsors
Telios Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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: 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 |
| 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 (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 |
Countries
Hungary, Italy, Poland, Russia, Ukraine, United Kingdom, United States
Outcome results
None listed