A Multicenter, Open Phase Ib Study of the Safety and Efficacy of BEBT-908 Combined With Drugs in the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- BEBT-908 for Injection
- Conditions
- Relapsed/Refractory Diffuse Large B-Cell Lymphoma
- Sponsor
- BeBetter Med Inc
- Enrollment
- 75
- Locations
- 1
- Primary Endpoint
- ORR
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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).
Detailed Description
This study sets up three cohorts, including BEBT-908 combined with R, BEBT-908 combined with R-ICE, and BEBT-908 combined with R-GemOx. 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. Namely, BEBT-908 monotherapy (alternative cohort 1), adjustment of BEBT-908 combined with GemOx administration regimen (alternative cohort 2). The study process for each participant includes a screening period, a treatment period, and a post-treatment follow-up period. During treatment, participants are evaluated for tumors every 6 weeks, follow up after termination of treatment with efficacy follow-up every 6 weeks for those without disease progression and survival follow-up every 3 months until disease progression (PD), death, emergence of intolerable toxicity, or withdrawal of informed consent (whichever occurred first).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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;
Exclusion Criteria
- •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;
Arms & Interventions
BEBT-908 combined with R
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.
Intervention: BEBT-908 for Injection
BEBT-908 combined with R
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.
Intervention: Rituximab Injection
BEBT-908 combined with R-GemOx
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.
Intervention: BEBT-908 for Injection
BEBT-908 combined with R-GemOx
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.
Intervention: Rituximab Injection
BEBT-908 combined with R-GemOx
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.
Intervention: Gemcitabine Hydrochloride for Injection
BEBT-908 combined with R-GemOx
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.
Intervention: Oxaliplatin Injection
BEBT-908 combined with R-ICE
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.
Intervention: BEBT-908 for Injection
BEBT-908 combined with R-ICE
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.
Intervention: Rituximab Injection
BEBT-908 combined with R-ICE
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.
Intervention: Etoposide Injection
BEBT-908 combined with R-ICE
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.
Intervention: Ifosfamide for Injection
BEBT-908 combined with R-ICE
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.
Intervention: Carboplatin Injection
BEBE-908 monotherapy (alternative cohort 1)
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.
Intervention: BEBT-908 for Injection
BEBT-908 combined with R-GemOx（alternative cohort 2）
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.
Intervention: BEBT-908 for Injection
BEBT-908 combined with R-GemOx（alternative cohort 2）
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.
Intervention: Rituximab Injection
BEBT-908 combined with R-GemOx（alternative cohort 2）
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.
Intervention: Gemcitabine Hydrochloride for Injection
BEBT-908 combined with R-GemOx（alternative cohort 2）
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.
Intervention: Oxaliplatin Injection
Outcomes
Primary Outcomes
ORR
Time Frame: Every 6 weeks，assessed up to 24 months.
Objective response rate
AE
Time Frame: From the first administration of the study drug to 28 days after the last administration of the study drug
Adverse event
Secondary Outcomes
- 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.)
- DCR(Every 6 weeks，assessed up to 24 months.)
- TTR(Every 6 weeks，assessed up to 24 months.)
- Tmax(From 1 hour before dosing on day 1 and day 12 of the first cycle to 48 hours after dosing, and from 1 hour before dosing on day 8 and day 10 of the first cycle (each cycle is 21 days).)
- Cmax(From 1 hour before dosing on day 1 and day 12 of the first cycle to 48 hours after dosing, and from 1 hour before dosing on day 8 and day 10 of the first cycle (each cycle is 21 days).)
- t1/2(From 1 hour before dosing on day 1 and day 12 of the first cycle to 48 hours after dosing, and from 1 hour before dosing on day 8 and day 10 of the first cycle (each cycle is 21 days).)
- AUC0-t(From 1 hour before dosing on day 1 and day 12 of the first cycle to 48 hours after dosing, and from 1 hour before dosing on day 8 and day 10 of the first cycle (each cycle is 21 days).)
- CL(From 1 hour before dosing on day 1 and day 12 of the first cycle to 48 hours after dosing, and from 1 hour before dosing on day 8 and day 10 of the first cycle (each cycle is 21 days).)