BR101801 in Adult Patients With Advanced Hematologic Malignancies( Phase I)
- Conditions
- B Cell LymphomaDiffuse Large B Cell LymphomaFollicular LymphomaChronic Lymphocytic LeukemiaSmall Lymphocytic LeukemiaMarginal Zone LymphomaWaldenstrom MacroglobulinemiaPeripheral T Cell Lymphoma
- Interventions
- Registration Number
- NCT04018248
- Lead Sponsor
- Boryung Pharmaceutical Co., Ltd
- Brief Summary
This is a Phase I-II, multi-center, open-label, FIH study comprising of 2 study parts (Phase Ia, 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 (RP2D) of BR101801 in subjects with relapsed/refractory B cell lymphoma, chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL), and peripheral T cell lymphoma (PTCL).
The Phase Ib (dose expansion) part of the study is designed to assess tumor response and safety in specific advanced relapsed/refractory Peripheral T-cell lymphoma(PTCL) at a dose of BR101801 identified in Phase Ia. Once the RP2D has been determined in Phase Ia (dose escalation), Phase Ib (dose expansion) will commence.
- Detailed Description
1. Phase Ia (Dose Escalation)
Primary Objectives
* 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.
SecondaryObjectives
* To characterize the plasma and urine PK of BR101801.
* To assess the preliminary antitumor activity of BR101801.
2. Phase Ib (Dose Expansion)
Primary Objectives
• To assess the safety and tolerability of BR101801 at the RP2D dose in subjects with relapsed/refractory Peripheral T-cell lymphoma (PTCL).
SecondaryObjectives
* 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.
OUTLINE: This is a Phase I, multi-center, open-label, FIH study. The safety monitoring committee(SMC) will be responsible for safety oversight.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Treatment (BR101801): Phase Ia (dose escalation) BR101801 (Phase Ia) Patients will receive BR101801 capsules orally, QD in 28-day cycles. The regimen may be changed to BID dosing based on emerging data. Treatment (BR101801):Phase Ib (dose expansion) BR101801 (Phase Ib) • Subjects with PTCL NOS, PTCL AITL, Nodal PTCL with TFH and PTCL FTCL
- Primary Outcome Measures
Name Time Method To determination of the MTD and RDE based on DLTs during Cycle 1 (Phase Ia ) 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) 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;
* ECGs;
* Physical examination
* ECOG performance status
- Secondary Outcome Measures
Name Time Method Cmax 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.
Ae 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
AUC(0-inf) 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) 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) 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
Trial Locations
- Locations (9)
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Jeollanam-do, Korea, Republic of
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul national university hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of