Study Comparing BEBT-908 Combined With R to SOC for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

NCT06792253 | Recruiting Phase 3

• 1 other identifier: GBMT-908-P08
• Study Type: interventional
• Target: 416
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, controlled, open-label Phase III clinical trial, aimed at evaluating the efficacy and safety of BEBT-908 combined with rituximab (R) compared to investigator-selected standard chemotherapy regimens \[Standard of Care (SOC)\] \[i.e., rituximab-gemcitabine-oxaliplatin (R-GemOx) or rituximab-ifosfamide-carboplatin-etoposide (R-ICE)\] for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL).

Conditions

Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Keywords

BEBT-908; Efficacy; Safety

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Defined as the time from the date of randomization to death due to any cause.

  Up to 48 months

Secondary Outcomes (6)

• Progression-Free Survival (PFS)

  Up to 48 months

• Overall Response Rate (ORR)

  Up to 48 months

• Overall Response Rate After Completion of Treatment (ORR-EoT)

  Up to 8 treatment cycles (Each cycle is 21 days.)

• Clinical Benefit Rate (CBR)

  Up to 48 months

• Duration of Response (DoR)

  Up to 48 months

Study Arms (2)

Experimental Group (BEBT-908 Combined With R)

EXPERIMENTAL

Ifupinostat Hydrochloride for Injection,18.5mg/m\^2 each time,is administered on days 1, 3, 5, 8, 10, and 12 of each cycle during cycles 1 to 8,with a 21-day cycle duration. After cycle 8, participants without PD enter a maintenance treatment phase that can last up to 24 months: Medication is administered on days 1, 3, 5, 8, 10, and 12 of each cycle, with a 21-day cycle duration, or as assessed by the investigator, medication is administered on days 1, 3, 5, 8, 10, and 12 of each cycle, with a 42-day cycle duration. Rituximab Injection,375 mg/m\^2 each time,is administered on day 1 of each cycle during cycles 1 to 8. After cycle 8, medication is administered on day 1 of every third cycle, with a 21-day cycle duration.

Drug: Ifupinostat Hydrochloride for Injection; Drug: Rituximab Injection

Control Group (R-GemOx or R-ICE)

ACTIVE COMPARATOR

Rituximab Injection,375mg/m\^2 each time,is administered on day 1 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles. Gemcitabine Hydrochloride for Injection,1g/m\^2 each time,is administered on day 2 of each cycle,with a 21-day cycle duration, for a total of 8 treatment cycles. Oxaliplatin Injection,100mg/m\^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles. Etoposide Injection,100mg/m\^2 each time,is administered on days 1, 2, and 3 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles. Ifosfamide for Injection,5000mg/m\^2 each time,is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles. Carboplatin Injection, with a single dose ≤800 mg \[calculated based on area under the curve(AUC)=5\],is administered on day 2 of each cycle, with a 21-day cycle duration, for a total of 8 treatment cycles.

Drug: Rituximab Injection; Drug: Gemcitabine Hydrochloride for Injection; Drug: Oxaliplatin Injection; Drug: Etoposide Injection; Drug: Ifosfamide for Injection; Drug: Carboplatin Injection

Interventions

Ifupinostat Hydrochloride for Injection DRUG

Ifupinostat Hydrochloride for Injection,dosage of administration:18.5mg/m\^2,frequency and duration of administration:Medication is administered on days 1, 3, 5, 8, 10, and 12 of each cycle,with a 21-day or 42-day cycle duration.

Also known as: BEBT-908 for Injection, CUDC-908

Experimental Group (BEBT-908 Combined With R)

Rituximab Injection DRUG

Rituximab Injection,dosage of administration:375 mg/m\^2,frequency and duration of administration:Medication is administered on day 1 of each cycle or every third cycle, with a 21-day cycle duration.

Also known as: IDEC-C2B8

Control Group (R-GemOx or R-ICE); Experimental Group (BEBT-908 Combined With R)

Gemcitabine Hydrochloride for Injection DRUG

Gemcitabine Hydrochloride for Injection,dosage of administration:1g/m\^2,frequency and duration of administration:Medication is administered on day 2 of each cycle, with a 21-day cycle duration.

Also known as: NSC 613327

Control Group (R-GemOx or R-ICE)

Oxaliplatin Injection DRUG

Oxaliplatin Injection,dosage of administration:100mg/m\^2,frequency and duration of administration:Medication is administered on day 2 of each cycle, with a 21-day cycle duration.

Also known as: NSC 266046

Control Group (R-GemOx or R-ICE)

Etoposide Injection DRUG

Etoposide Injection,dosage of administration:100mg/m\^2,frequency and duration of administration:Medication is administered on days 1,2,and 3 of each cycle, with a 21-day cycle duration.

Also known as: VP-16213

Control Group (R-GemOx or R-ICE)

Ifosfamide for Injection DRUG

Ifosfamide for Injection,dosage of administration:5000mg/m\^2,frequency and duration of administration:Medication is administered on day 2 of each cycle, with a 21-day cycle duration.

Also known as: NSC109724

Control Group (R-GemOx or R-ICE)

Carboplatin Injection DRUG

Carboplatin Injection,,dosage of administration:single dose ≤800 mg (calculated based on AUC=5),frequency and duration of administration:Medication is administered on day 2 of each cycle, with a 21-day cycle duration.

Also known as: NSC 241240

Control Group (R-GemOx or 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 has been fully informed and is willing to sign the Informed Consent Form (ICF).
• Age is ≥18 years and ≤75 years, both men and women are eligible.
• Pathologically diagnosed as diffuse large B-cell lymphoma according to the 2022 World Health Organization classification, confirmed by central pathology review (Patients who relapse after more than one year need to undergo tissue biopsy again to confirm the pathological diagnosis.).
• Measurable lesions \[The criteria for measurable lesions are: the longest diameter of lymph node lesions measured by enhanced Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) is greater than 15 mm, and the longest diameter of extranodal lesions is greater than 10 mm.\] assessed by Positron Emission Tomography/Computed Tomography (PET-CT) and Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) according to the Lugano 2014 criteria .
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Expected survival \>12 weeks.
• Organ function levels must meet the following requirements:
• Peripheral blood:
• Absolute neutrophil count (ANC) ≥1.0×10\^9/L;
• Hemoglobin (HGB) ≥80g/L;
• Platelet count (PLT) ≥100×10\^9/L;
• Liver and kidney function:
• Serum total bilirubin ≤1.5×Upper Limit of Normal (ULN) (for patients with Gilbert syndrome, total bilirubin \<3.0×ULN with direct bilirubin within normal range);
• Serum creatinine \<1.5×ULN;
• Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) ≤2.5×ULN (≤5×ULN if there is liver involvement).

You may not qualify if:

• Known severe allergy to the study drug or any of its excipients;
• Due to the potential genotoxicity, mutagenicity, and teratogenicity of the study drug, the following subjects should be excluded:
• Men and women who have not undergone in vitro preservation of sperm or oocytes and plan to have children within 5 years, unless subsequent studies confirm reproductive safety;
• Pregnant or breastfeeding women;
• Primary central nervous system lymphoma;
• DLBCL with active central nervous system brain metastases or meningeal involvement at the time of screening;
• Other active malignant tumors that require treatment and may interfere with the study.
• Treatment history before the trial:
• Received other small molecule targeted drug therapy within 2 weeks before enrollment;
• Previously received BEBT-908 or R-ICE and R-GemOx therapy before enrollment;
• Underwent autologous hematopoietic stem cell transplantation within 3 months before enrollment;
• Received radiotherapy that affects the evaluation of the efficacy of this study within 3 months before enrollment, or local supportive radiotherapy that affects the subject's bone marrow function;
• Underwent myelosuppressive chemotherapy or biological therapy within 3 weeks before enrollment;
• Used traditional Chinese medicine and patent medicine with antitumor effects within 2 weeks before enrollment;
• Underwent major surgery (Referring to the Level 3 and Level 4 surgeries as stipulated in the "Administrative Measures for the Clinical Application of Medical Technologies" implemented on May 1, 2009.) other than tumor biopsy within 4 weeks before enrollment, or the side effects of the surgery have not yet 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

Injections; BEBT-908; 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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomly assigned in a 1:1 ratio to either the experimental group (BEBT-908 combined with R) or the control group \[investigator-selected standard chemotherapy regimen (R-GemOx or R-ICE)\].

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: January 24, 2025
• Study Start: January 6, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029
• Last Updated: January 24, 2025

Record last verified: 2025-01

Locations

CN (1)