BR101801 in Adult Patients With Advanced Hematologic Malignancies(Phase I)

NCT04018248 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BR-101801-CT-101
• Study Type: interventional
• Target: 26
• Locations: 2 countries
• Sites: 9

Brief Summary

This is a Phase I, 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• To determination of the MTD and RDE based on DLTs during Cycle 1 (Phase Ia)

  The recommended dose is determined by the number of patients who experience a dose limiting toxicity (DLT).

  From baseline to Week 4

• 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)

  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

  through study completion, and about average of 1 year

Secondary Outcomes (5)

• Cmax

  Cycle1( each cycle is 28 days) Day 1 and Cycle 1( each cycle is 28 days) Day 15

• AUC(0-inf)

  Cycle1( each cycle is 28 days) Day 1

• 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

• 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

• 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

Study Arms (2)

Treatment (BR101801): Phase Ia (dose escalation)

EXPERIMENTAL

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)

Treatment (BR101801):Phase Ib (dose expansion)

EXPERIMENTAL

• Subjects with PTCL NOS, PTCL AITL, Nodal PTCL with TFH and PTCL FTCL

Drug: BR101801 (Phase Ib)

Interventions

BR101801 (Phase Ia) DRUG

Phase Ia (dose escalation):25 mg capsules and 100 mg capsules Planned doses are 50, 100, 200, 325, and 450 mg.

Treatment (BR101801): Phase Ia (dose escalation)

BR101801 (Phase Ib) DRUG

Phase Ib (dose expansion):25 and 100 mg capsules Doses administered will be determined from Phase Ia data.

Treatment (BR101801):Phase Ib (dose expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must sign an informed consent document
• Female or male patients aged ≥ 18 years.
• ECOG performance status ≤ 2.
• Life expectancy more than 3 months.
• Phase Ia:Patients with relapsed and/or refractory relapsed/refractory B-cell lymphoma, CLL/SLL, and PTCL diagnosed with World Health Organization (WHO) classification
• Phase Ib: Subjects with PTCL NOS, PTCL AITL, Nodal PTCL with TFH and PTCL FTCL.
• Patients have measurable disease based on the appropriate tumor type criteria( Phase Ib only)
• Have a current need for systemic therapy, the assessment of the investigator.
• An archival or fresh tumor tissue (ie, tissue block or series of at least 5 slides, up to 15 slides) is required and should be provided during the Screening Visit for Lymphoma subjects. Local review of pathology is required for study entry in Phase Ib only.
• Phase Ia subjects should be prepared to undergo a fresh tumor biopsy during the study (tumor biopsies will be obtained from 1 to 2 subjects per cohort in Phase Ia).
• Subject having laboratory values defined as:
• Creatinine clearance (measured or calculated per institutional standard practice) ≥ 60 mL/min. GFR can also be used in place of creatinine clearance.
• Total bilirubin \< 1.5 × ULN, except for subjects with Gilbert's syndrome who are excluded if total bilirubin \> 3.0 × ULN or direct bilirubin \< 1.5 × ULN.
• ALT \< 2.5 × ULN, except for subjects who have tumor involvement of the liver, who are included if ALT \< 5 × ULN.
• AST \< 2.5 × ULN, except for subjects that have tumor involvement of the liver, who are included if AST \< 5 × ULN.

You may not qualify if:

• Presence of overt leptomeningeal or active CNS metastases, or CNS metastases that require local CNS-directed therapy or increasing doses of corticosteroids within the prior 2 weeks. Patients with treated brain metastases should be neurologically stable and off steroids for at least 2 weeks before administration of any study treatment.
• Impaired cardiac function or clinically significant cardiac disease
• Patients with interstitial pneumonia or history of drug-induced interstitial pneumonia/pneumonitis.
• Human immunodeficiency virus (HIV) infection.
• Patients who are positive for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (HCVAb).
• Chronic liver disease or chronic hepatitis
• Any gastrointestinal disorders interfering with study drug absorption or are unable to swallow tablets or capsules.
• Malignant disease, other than that being treated in this study.
• Prior PI3K inhibitor will be accepted in the dose escalation part of the study (Phase Ia) only.
• For patients with lymphoma:
• Systemic antineoplastic therapy (including cytotoxic chemotherapy, alfa-interferon \[INF\], and toxin immunoconjugates) or any experimental therapy within 3 weeks or 5 half lives, whichever is shorter, before the first dose of study treatment.
• Therapy with tyrosine kinase inhibitor within 5 half-lives before the first dose of study treatment.
• Unconjugated monoclonal antibody therapies \< 6 weeks before the first dose of study treatment.
• Patients receiving systemic chronic steroid therapy or any immunosuppressive therapy (≥ 10 mg/day prednisone or equivalent).
• Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.

Sponsors & Collaborators

• Boryung Pharmaceutical Co., Ltd: lead

Study Sites (9)

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Location

Inje University Busan Paik Hospital

Busan, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul national university hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Waldenstrom Macroglobulinemia; Lymphoma, T-Cell, Peripheral

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoma, T-Cell

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Jorge Chaves, M.D, Ph.D

  Northwest Medical Specialities, PLLC

  PRINCIPAL INVESTIGATOR

• Emily Curran, M.D, Ph.D

  University of Cincinnati

  PRINCIPAL INVESTIGATOR

• JS Kim, M.D, Ph.D

  Severance Hospital, Yonsei University Health System

  PRINCIPAL INVESTIGATOR

• EY Lee, M.D, M.S

  National Cancer Center

  PRINCIPAL INVESTIGATOR

• JO Lee, M.D, Ph.D

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

• DH Yang, M.D, Ph.D

  Chonnam National University Hospital

  PRINCIPAL INVESTIGATOR

• WS Lee, M.D, Ph.D

  Inje University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: July 12, 2019
• Study Start: April 21, 2020
• Primary Completion: September 21, 2023
• Study Completion: September 21, 2023
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (8); US (1)