BR101801 in Adult Patients With Advanced Hematologic Malignancies( Phase I)
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|ClinicalTrials.gov Identifier: NCT04018248|
Recruitment Status : Not yet recruiting
First Posted : July 12, 2019
Last Update Posted : July 16, 2019
This is a Phase I, multi-center, open-label, FIH study comprising of 2 study parts (Phase Ia and Phase Ib).
The Phase Ia (dose escalation) part of the study is designed to determine the safety, tolerability, and maximum tolerated dose (MTD)/recommended dose for expansion (RDE) of BR101801 in patients with relapsed/refractory advanced hematologic malignancies except acute leukemia and multiple myeloma.
The Phase Ib (dose expansion) part of the study is designed to assess tumor response and safety in specific advanced relapsed/refractory hematologic malignances at a dose of BR101801 identified in Phase Ia. Once the RDE has been determined in Phase Ia (dose escalation), Phase Ib (dose expansion) will commence, and 3 groups will be recruited in parallel.
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B Cell Lymphoma Follicular Lymphoma Chronic Lymphocytic Leukemia Small Lymphocytic Leukemia B Cell Lymphoma Marginal Zone Lymphoma Waldenstrom Macroglobulinemia Peripheral T Cell Lymphoma||Drug: BR101801 (Phase Ia) Drug: BR101801 (Phase Ib)||Phase 1|
Phase Ia (Dose Escalation)
- To assess the safety and tolerability of BR101801 in patients with relapsed/refractory B-cell lymphoma, CLL/SLL, and PTCL.
- To assess DLT and to determine the MTD and/or the RDE dose for BR101801 when administered orally on a daily schedule in 4-week cycles until disease progression.
- To characterize the plasma and urine PK of BR101801.
- To assess the preliminary antitumor activity of BR101801.
- To characterize the PD of BR101801.
- To explore BR101801 metabolites.
- Phase Ib (Dose Expansion)
•To assess the safety and tolerability of BR101801 at the RDE dose in patients with relapsed and/or refractory B-cell lymphoma, CLL/SLL, and PTCL.
- To assess clinical activity of BR101801 when administered orally on a daily schedule in 4-week cycles until disease progression.
- To assess the plasma PK of BR101801
- To assess the PD of BR101801.
- To explore BR101801 metabolites.
OUTLINE:This is a Phase I, multi-center, open-label, FIH study . Patients in Phase Ia and Phase Ib will receive BR101801 capsules orally and safety monitoring committee (SMC) will be responsible for safety oversight.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I, Open-label, Multi-center, Dose Escalation, and Expansion Study of BR101801 in Adult Patients With Advanced Hematologic Malignancies|
|Estimated Study Start Date :||November 2019|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||February 2024|
Experimental: Treatment ( BR101801):Phase Ia (dose escalation)
Patients will receive BR101801 capsules orally, QD in 28-day cycles. The regimen may be changed to BID dosing based on emerging data.
Drug: BR101801 (Phase Ia)
Phase Ia (dose escalation):25 mg capsules and 100 mg capsules Planned doses are 50, 100, 200, 325, and 450 mg.
Experimental: Treatment ( BR101801):Phase Ib (dose expansion)
Group A: Patients with diffuse large B-cell lymphoma (DLBCL) including MYC-altered DLBCL
Group B: Patients with follicular lymphoma.
Group C: Patients with chronic lymphocytic leukemia/small lymphocytic leukemia, other B-cell lymphoma such as, but not limited to mantle cell lymphoma, marginal zone lymphoma, Waldenstrom's macroglobulinemia, or PTCL
Drug: BR101801 (Phase Ib)
Phase Ib (dose expansion):25 and 100 mg capsules Doses administered will be determined from Phase Ia data.
- To determination of the MTD and RDE based on DLTs during Cycle 1 (Phase Ia ) [ Time Frame: From baseline to Week 4 ]The recommended dose is determined by the number of patients who experience a dose limiting toxicity (DLT).
- Number of Participants With Adverse Events (AE) as a Measure of Safety and Tolerability of BR101801 when administered at the MTD or recommended dose (Phase Ia and Ib) [ Time Frame: through study completion, and about average of 1 year ]
To evaluate safety and tolerability the aggregate review will include but is not limited to:
- CTCAE TEAEs, treatment-related TEAEs, Grade 3 or higher TEAEs, Grade 3 or higher treatment-related TEAEs, serious treatment-related TEAEs, and TEAEs leading to death.
- Laboratory results;
- Vital signs;
- Physical examination
- ECOG performance status
- Cmax [ Time Frame: Cycle1( each cycle is 28 days) Day 1 and Cycle 1( each cycle is 28 days) Day 15 ]Maximum concentration obtained directly from the observed concentration versus time data.
- AUC(0-inf) [ Time Frame: Cycle1( each cycle is 28 days) Day 1 ]Area under the plasma concentration-time curve from time zero extrapolated to infinity, calculated by linear up/log down trapezoidal summation
- AUC(0-last) [ Time Frame: Cycle1( each cycle is 28 days) Day 1 and Cycle 1( each cycle is 28 days) Day 15, Pre-dose to 24 hours after dosing ]Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration
- AUC(0-tau) [ Time Frame: Cycle1( each cycle is 28 days) Day 1 and Cycle 1( each cycle is 28 days) Day 15, dosing interval: 24 or 12 hours ]Area under the plasma concentration-time curve from time zero during a dosing interval
- Ae [ Time Frame: Cycle 1( each cycle is 28 days)Day 15, Pre-dose to 12 hours for BID dosing and Pre-dose to 24 hours for QD dosing ]Cumulative amount of unchanged drug excreted in urine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04018248
|Contact: Jayhyuk Myung||+82-31-491-2271 (Ext. 501)||email@example.com|
|Contact: Evertin Kimfirstname.lastname@example.org|
|Principal Investigator:||TM Kim, M.D, Ph.D||Seoul National University Hospital|
|Principal Investigator:||SJ Kim, M.D, Ph.D||Samsung Medical Center|
|Principal Investigator:||DH Yoon, M.D, Ph.D||Asan Medical Center|