Brief Title
BR101801 in Adult Patients With Advanced Hematologic Malignancies( Phase I-II)
Official Title
A Phase I-II, Open-label, Multi-center, Dose Escalation, and Expansion Study of BR101801 in Adult Patients With Advanced Hematologic Malignancies
Brief Summary
This is a Phase I-II, multi-center, open-label, FIH study comprising of 3 study parts (Phase Ia, Phase Ib, and Phase II). 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 B-cell lymphoma, CLL/SLL, and PTCL at a dose of BR101801 identified in Phase Ia. The Phase II part is designed to examine the tumor responsiveness in the subjects with two forms of PTCL: PTCL NOS and PTCL AITL.
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 B cell lymphoma, CLL/SLL, and 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. 3. Phase II Primary Objectives • To further assess the activity, safety, and tolerability of BR101801 at the RP2D dose in subjects with relapsed/refractory PTCL. SecondaryObjectives • To assess the plasma PK of BR101801. OUTLINE: This is a Phase I-II, multi-center, open-label, FIH study. The safety monitoring committee (SMC) will be responsible for safety oversight.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
To determination of the MTD and RDE based on DLTs during Cycle 1 (Phase Ia )
Secondary Outcome
Cmax
Condition
Diffuse Large B Cell Lymphoma
Intervention
BR101801 (Phase Ia)
Study Arms / Comparison Groups
Treatment (BR101801):Phase Ia (dose escalation)
Description: Patients will receive BR101801 capsules orally, QD in 28-day cycles. The regimen may be changed to BID dosing based on emerging data.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
90
Start Date
April 21, 2020
Completion Date
February 2024
Primary Completion Date
December 2023
Eligibility Criteria
1. Patients must sign an informed consent document 2. Female or male patients aged ≥ 18 years. 3. ECOG performance status ≤ 2. 4. Life expectancy more than 3 months. 5. Phase Ia:Patients with relapsed and/or refractory relapsed/refractory B-cell lymphoma, CLL/SLL, and PTCL diagnosed with World Health Organization (WHO) classification 6. Phase Ib: - Group A: Subjects with DLBCL including MYC-altered DLBCL and transformed DLBCL. - Group B: Subjects with PTCL NOS and PTCL AITL. - Group C: Subjects with CLL/SLL, other B-cell lymphoma such as, but not limited to, mantle cell lymphoma, marginal zone lymphoma, Waldenstrom macroglobulinemia, or PTCL. 7. Phase II: Subjects with relapsed and/or refractory PTCL NOS and PTCL AITL (WHO classification) who have received standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists and those who have already been recruited into the Phase Ib portion of the study. Patients have measurable disease based on the appropriate tumor type criteria( Phase Ib only) 1. 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. 2. Impaired cardiac function or clinically significant cardiac disease 3. Patients with interstitial pneumonia or history of drug-induced interstitial pneumonia/pneumonitis. 4. Human immunodeficiency virus (HIV) infection. 5. Patients who are positive for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (HCVAb). 6. Chronic liver disease or chronic hepatitis 7. Any gastrointestinal disorders interfering with study drug absorption or are unable to swallow tablets or capsules. 8. Malignant disease, other than that being treated in this study. 9. For patients with lymphoma: - Systemic antineoplastic therapy or any experimental therapy within 3 weeks or 5 half lives, whichever is shorter, before the first dose of study treatment. 11.Patients receiving systemic chronic steroid therapy or any immunosuppressive therapy (≥ 10 mg/day prednisone or equivalent). 12.Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. 13.Use of hematopoietic colony-stimulating growth factors, thrombopoietin mimetics, or erythroid-stimulating agents ≤ 2 weeks prior to start of study drug. 14.Patients with a history of stroke or having active neurological symptoms, with the exception of chronic conditions which, in the opinion of the neurologist, Investigator, and the Sponsor, would not impact ongoing neurologic assessments while on study treatment. 15.Active infection requiring systemic or antiviral antibiotic therapy. 16.Major surgery within 2 weeks of the first dose of study treatment 17.Radiotherapy within 2 weeks of the first dose of study drug, except for palliative radiotherapy to a limited-field, such as for the treatment of bone pain or a focally painful tumor mass. 18.Presence of CTCAE ≥ Grade 2 toxicity due to prior cancer therapy. 19.Participation in an interventional, investigational study within 2 weeks or 5 half-lives, whichever is shorter, of the first dose of study treatment. 20.Any medical condition that would, in the Investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns, compliance with clinical study procedures, or interpretation of study results.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
TM Kim, M.D, Ph.D, +82-2-708-8204, [email protected]
Location Countries
Korea, Republic of
Location Countries
Korea, Republic of
Administrative Informations
NCT ID
NCT04018248
Organization ID
BR-101801-CT-101
Responsible Party
Sponsor
Study Sponsor
Boryung Pharmaceutical Co., Ltd
Study Sponsor
TM Kim, M.D, Ph.D, Principal Investigator, Seoul National University Hospital
Verification Date
November 2021