Study of BEBT-908 Combined With Drugs in the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

NCT06164327 | Unknown Phase 1

• 1 other identifier: GBMT-908-P06
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open Phase Ib clinical study to evaluate the safety,efficacy and pharmacokinetics of BEBT-908 combined with Rituximab (R) or combined with Rituximab-Gemcitabine-Oxaliplatin (R-GemOx) or combined with Rituximab-Ifosfamide-Carboplatin-Etoposide (R-ICE) in the treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL).

Conditions

Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Keywords

BEBT-908; Drug combination; Safety; Efficacy

Outcome Measures

Primary Outcomes (2)

• ORR

  Objective response rate

  Every 6 weeks，assessed up to 24 months.

• AE

  Adverse event

  From the first administration of the study drug to 28 days after the last administration of the study drug

Secondary Outcomes (12)

• ORR-EoT

  Every 6 weeks，assessed up to 6 treatment cycles (each cycle is 21 days).

• PFS

  From date of administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months

• OS

  From date of administration until date of death from any cause, assessed up to 24 months.

• CBR

  Every 6 weeks，assessed up to 24 months.

• DOR

  Every 6 weeks，assessed up to 24 months.

Study Arms (5)

BEBT-908 combined with R

EXPERIMENTAL

BEBT-908 for Injection,dosage of administration:22.5mg/m\^2，frequency and duration of administration:on the 1st,3rd,5th,8th,10th and 12th days of each cycle in the 1st to 6th cycles,and 21 days as a cycle. Rituximab Injection,dosage of administration:375 mg/m\^2,frequency and duration of administration:on the 1st day of each cycle, and 21 days as a cycle.

Drug: BEBT-908 for Injection; Drug: Rituximab Injection

BEBT-908 combined with R-GemOx

EXPERIMENTAL

BEBT-908 for Injection,dosage of administration:15mg/m\^2，frequency and duration of administration:on the 1st,3rd,5th,8th,10th and 12th days of each cycle in the 1st to 6th cycles,and 21 days as a cycle. Rituximab Injection,dosage of administration:375 mg/m\^2,frequency and duration of administration:on the 1st day of each cycle in the 1st to 6th cycles, and 21 days as a cycle. Gemcitabine Hydrochloride for Injection，dosage of administration:1g/m\^2,frequency and duration of administration:on the 2nd day of each cycle in the 1st to 6th cycles, and 21 days as a cycle. Oxaliplatin Injection,dosage of administration:100mg/m\^2,frequency and duration of administration:on the 2nd day of each cycle in the 1st to 6th cycles, and 21 days as a cycle.

Drug: BEBT-908 for Injection; Drug: Rituximab Injection; Drug: Gemcitabine Hydrochloride for Injection; Drug: Oxaliplatin Injection

BEBT-908 combined with R-ICE

EXPERIMENTAL

BEBT-908 for Injection,dosage of administration:15mg/m\^2，frequency and duration of administration:on the 1st,3rd,5th,8th,10th and 12th days of each cycle in the 1st to 6th cycles,and 21 days as a cycle. Rituximab Injection,dosage of administration:375 mg/m\^2,frequency and duration of administration:on the 1st day of each cycle in the 1st to 6th cycles, and 21 days as a cycle. Etoposide Injection,dosage of administration:100mg/m\^2，frequency and duration of administration:on the 1st,2nd and 3rd days of each cycle in the 1st to 6th cycles,and 21 days as a cycle. Ifosfamide for Injection,dosage of administration:5000mg/m\^2,frequency and duration of administration:on the 2nd day of each cycle in the 1st to 6th cycles, and 21 days as a cycle. Carboplatin Injection，dosage of administration:based on AUC=5, single dose ≤800 mg，frequency and duration of administration:on the 2nd day of each cycle in the 1st to 6th cycles, and 21 days as a cycle.

Drug: BEBT-908 for Injection; Drug: Rituximab Injection; Drug: Etoposide Injection; Drug: Ifosfamide for Injection; Drug: Carboplatin Injection

BEBE-908 monotherapy (alternative cohort 1)

EXPERIMENTAL

BEBT-908 for Injection,dosage of administration:22.5mg/m\^2，frequency and duration of administration:on the 1st,3rd,5th,8th,10th and 12th days of each cycle in the 1st to 6th cycles,and 21 days as a cycle.

Drug: BEBT-908 for Injection

BEBT-908 combined with R-GemOx（alternative cohort 2）

EXPERIMENTAL

BEBT-908 for Injection,dosage of administration:22.5mg/m\^2，frequency and duration of administration:on the 1st,3rd,5th,8th,10th and 12th days of each cycle in the 1st to 2nd cycles,and 21 days as a cycle. Rituximab Injection,dosage of administration:375 mg/m\^2,frequency and duration of administration:on the 1st day of each cycle in the 3rd to 6th cycles, and 21 days as a cycle. Gemcitabine Hydrochloride for Injection，dosage of administration:1g/m\^2,frequency and duration of administration:on the 2nd day of each cycle in the 3rd to 6th cycles, and 21 days as a cycle. Oxaliplatin Injection,dosage of administration:100mg/m\^2,frequency and duration of administration:on the 2nd day of each cycle in the 3rd to 6th cycles, and 21 days as a cycle.

Drug: BEBT-908 for Injection; Drug: Rituximab Injection; Drug: Gemcitabine Hydrochloride for Injection; Drug: Oxaliplatin Injection

Interventions

BEBT-908 for Injection DRUG

BEBT-908 for Injection,dosage of administration:15mg/m\^2 or 22.5mg/m\^2，frequency and duration of administration:on the 1st,3rd,5th,8th,10th and 12th days of each cycle,and 21 days as a cycle.

Also known as: CUDC-908

BEBE-908 monotherapy (alternative cohort 1); BEBT-908 combined with R; BEBT-908 combined with R-GemOx; BEBT-908 combined with R-GemOx（alternative cohort 2）; BEBT-908 combined with R-ICE

Rituximab Injection DRUG

Rituximab Injection,dosage of administration:375 mg/m\^2,frequency and duration of administration:on the 1st day of each cycle, and 21 days as a cycle.

Also known as: IDEC-C2B8

BEBT-908 combined with R; BEBT-908 combined with R-GemOx; BEBT-908 combined with R-GemOx（alternative cohort 2）; BEBT-908 combined with R-ICE

Gemcitabine Hydrochloride for Injection DRUG

Gemcitabine Hydrochloride for Injection，dosage of administration:1g/m\^2,frequency and duration of administration:on the 2nd day of each cycle, and 21 days as a cycle.

Also known as: NSC 613327

BEBT-908 combined with R-GemOx; BEBT-908 combined with R-GemOx（alternative cohort 2）

Oxaliplatin Injection DRUG

Oxaliplatin Injection，dosage of administration:100mg/m\^2,frequency and duration of administration:on the 2nd day of each cycle, and 21 days as a cycle.

Also known as: NSC 266046

BEBT-908 combined with R-GemOx; BEBT-908 combined with R-GemOx（alternative cohort 2）

Etoposide Injection DRUG

Etoposide Injection,dosage of administration:100mg/m\^2，frequency and duration of administration:on the 1st,2nd and 3rd days of each cycle,and 21 days as a cycle.

Also known as: VP-16213

BEBT-908 combined with R-ICE

Ifosfamide for Injection DRUG

Ifosfamide for Injection,dosage of administration:5000mg/m\^2,24 hours of continuous intravenous drip，frequency and duration of administration:on the 2nd day of each cycle, and 21 days as a cycle.

Also known as: NSC109724

BEBT-908 combined with R-ICE

Carboplatin Injection DRUG

Carboplatin Injection，dosage of administration:based on AUC=5, single dose ≤800 mg，frequency and duration of administration:on the 2nd day of each cycle, and 21 days as a cycle.

Also known as: NSC 241240

BEBT-908 combined with R-ICE

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject is willing to sign the informed consent form (ICF) after comprehensive understanding;
• Age ≥18 years and ≤75 years, both male and female;
• The pathology was confirmed as diffuse large B-cell lymphoma according to the 2016 World Health Organization classification definition;
• Evaluation by Positron Emission Computed Tomography (PET-CT) or Computed Tomography (CT) or Magnetic resonance imaging (MRI) using Lugano 2014 standard, with measurable lesion injection;
• Must have recurrent or refractory diffuse large B-cell lymphoma after at least 1 systemic therapy, and at least 1 systemic therapy included CD20 antibody;
• Eastern Cooperative Oncology Group (ECOG) scores 0-2 points;
• Life expectancy \>12 weeks;
• The level of organ function must meet the following requirements:
• Peripheral blood:
• Absolute neutrophil count (ANC) ≥1000/μL;
• Hemoglobin (HGB) ≥8g/dL;
• Platelet count (PLT) ≥100,000/μL;
• Liver function:
• Serum total bilirubin ≤1.5×ULN (for patients with Gilbert syndrome, total bilirubin \<3.0×ULN and Direct bilirubin within normal range);
• Serum creatinine \<1.5×ULN;

You may not qualify if:

• Known severe allergy to the investigational drug or any of its excipients;
• Due to the possibility of genotoxicity, mutagenicity and teratogenicity of the investigational drug, the following subjects should be excluded:
• Men and women who have not had sperm or egg preservation in vitro before the trial and plan to have another child within 5 years unless subsequent studies confirm reproductive safety;
• Pregnant or lactating women;
• Primary central nervous system lymphoma or lymphoma invading the central nervous system;
• Previous chronic lymphoma transformation (such as Richter syndrome, prelymphocytic leukemia, etc.);
• There are other active malignant tumors requiring treatment that may interfere with the study;
• Pre-trial treatment:
• Received any persistent or intermittent PI3K inhibitor and HDAC inhibitor prior to enrollment or received other small-molecule targeted drug therapy within 2 weeks;
• Received BEBT-908 (not allowed to be in all cohorts) or R-ICE (not allowed to be in cohorts with BEBT-908+R-ICE) or R-GemOx (not allowed to be in cohorts with BEBT-908+R-GemOx) prior to enrollment;
• Autologous hematopoietic stem cell transplantation within 3 months before enrollment;
• Received radiotherapy that affected the evaluation of the efficacy of the study or local supportive radiotherapy that affected the bone marrow function of the subjects within 3 months before enrollment;
• Received myelosuppressive chemotherapy or biotherapy within 3 weeks prior to enrollment;
• Used Chinese medicines and proprietary Chinese medicines with anti-tumor effects within 2 weeks before enrollment;
• Undergone major surgery other than tumor biopsy within 4 weeks prior to enrollment, or the side effects of surgery had not stabilized;

Sponsors & Collaborators

• BeBetter Med Inc: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

BEBT-908; Injections; Rituximab; Gemcitabine; Oxaliplatin; Etoposide; Ifosfamide; Carboplatin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines

Study Officials

• Yuankai Shi, Phd

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kegang Jiang, Master

CONTACT

+86-18664786382; kjiang@bebettermed.com

Study Design

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

Model Details: The study sets up three cohorts of BEBT-908 combined with different drugs.The researchers decide whether to terminate the cohort study according to the safety and tolerability results of each cohort during the first cycle of medication. If the participants in the above three cohorts are unable to receive the treatment during the first cycle of medication, two alternative cohort studies will be conducted.

Study Record Dates

• First Submitted: November 22, 2023
• First Posted: December 11, 2023
• Study Start: December 1, 2023
• Primary Completion: October 31, 2025
• Study Completion: November 5, 2025
• Last Updated: December 11, 2023

Record last verified: 2023-12

Locations

CN (1)