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

Brief Title

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

Official Title

A Phase I, 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 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.
    

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

30

Start Date

April 21, 2020

Completion Date

March 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: Subjects with PTCL NOS, PTCL AITL, Nodal PTCL with TFH and PTCL FTCL.

          7. Patients have measurable disease based on the appropriate tumor type criteria( Phase
             Ib only)

          8. Have a current need for systemic therapy, the assessment of the investigator.

          9. 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.

         10. 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).

         11. 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.

               -  Absolute neutrophil count > 1.0 × 109/L.

               -  Platelet count > 75 × 109/L.

               -  Hemoglobin > 8 g/dL.

        

          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. Prior PI3K inhibitor will be accepted in the dose escalation part of the study (Phase
             Ia) only.

         10. 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.

         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. Subjects with active CMV infection.

         17. Subjects receiving moderate or potent CYP3A4 inhibitors or inducers and are unable to
             withdraw until 2 weeks or 5 times longer than the half-life, whichever is shorter,
             before the first dose of study treatment.

         18. Major surgery within 2 weeks of the first dose of study treatment (mediastinoscopy,
             insertion of a central venous access device, and insertion of a feeding tube are not
             considered major surgery).

         19. Radiotherapy within 2 weeks of the first dose of study treatment, except for
             palliative radiotherapy to a limited-field, such as for the treatment of bone pain or
             a focally painful tumor mass.

         20. Presence of CTCAE ≥ Grade 2 toxicity (except alopecia, peripheral neuropathy, and
             ototoxicity, which are excluded if ≥ CTCAE Grade 3) due to prior cancer therapy.

         21. Participation in an interventional, investigational study within 2 weeks or 5
             half-lives, whichever is shorter, of the first dose of study treatment.

         22. Any medical condition that would, in the Investigator's judgment, prevent the
             subject's participation in the clinical study due to safety concerns, compliance with
             clinical study procedures, or interpretation of study results.

         23. Pregnant or lactating women, where pregnancy is defined as the state of a female after
             conception and until the termination of gestation, confirmed by a positive human
             chorionic gonadotropin laboratory test.
      

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

January 2023