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

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 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

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