BELIEVE-01: A Study of Orelabrutinib Plus R-CHOP in Treatment-naïve Patients With MCD Subtype Diffuse Large B-cell Lymphoma

Sponsor

Beijing InnoCare Pharma Tech Co., Ltd. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05234684

Collaborator

(none)

150

Enrollment

Location

Arms

Anticipated Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of orelabrutinib combined with R-CHOP regimen versus placebo with R-CHOP in the treatment of treatment-naïve patients with MCD subtype DLBCL.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma (DLBCL)	Drug: Orelabrutinib + R-CHOP Drug: Placebo + R-CHOP	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase III, Randomized, Double-blind, Placebo-controlled, Multicenter Study Evaluating the Efficacy and Safety of Orelabrutinib Plus R-CHOP Versus Placebo Plus R-CHOP in Treatment-naïve Patients With MCD Subtype DLBCL

Anticipated Study Start Date :

Aug 30, 2022

Anticipated Primary Completion Date :

Jun 30, 2023

Anticipated Study Completion Date :

Dec 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Orelabrutinib+ R-CHOP Participants will receive 150 mg of oral orelabrutinib once daily with R-CHOP on day 1 of each cycle (21 days).	Drug: Orelabrutinib + R-CHOP The orelabrutinib is a white, round, uncoated tablet. The R-CHOP include rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison. Other Names: ICP-022+ R-CHOP
Placebo Comparator: Placebo+ R-CHOP Participants will receive 150 mg placebo once daily with R-CHOP on day 1 of each cycle (21 days).	Drug: Placebo + R-CHOP The placebo is a white, round, uncoated tablet. The R-CHOP include rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison.

Arm

Intervention/Treatment

Experimental: Orelabrutinib+ R-CHOP

Participants will receive 150 mg of oral orelabrutinib once daily with R-CHOP on day 1 of each cycle (21 days).

Drug: Orelabrutinib + R-CHOP

The orelabrutinib is a white, round, uncoated tablet. The R-CHOP include rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison.

Other Names:

ICP-022+ R-CHOP

Placebo Comparator: Placebo+ R-CHOP

Participants will receive 150 mg placebo once daily with R-CHOP on day 1 of each cycle (21 days).

Drug: Placebo + R-CHOP

The placebo is a white, round, uncoated tablet. The R-CHOP include rituximab, cyclophosphamide, doxorubicin, vincristine, and prednison.

Outcome Measures

Primary Outcome Measures

Progression free survival (PFS) [Up to 3 years and 9 months]
Progression free survival (PFS) accessed by independent review committee (IRC)
Complete response rate (CRR) by independent review committee (IRC) [Up to 3 years and 9 months]
Complete response rate (CRR) at the completion of combination therapy accessed by independent review committee (IRC)

Secondary Outcome Measures

Complete response rate (CRR) by investigator [Up to 3 years and 9 months]
Complete response rate (CRR) at the completion of combination therapy accessed by investigator
Overall response rate (ORR) by independent review committee (IRC) and investigator [Up to 3 years and 9 months]
Overall response rate (ORR) accessed by independent review committee (IRC) and investigator
Overall response rate (ORR) at the completion of combination therapy by independent review committee (IRC) and investigator [Up to 3 years and 9 months]
Overall response rate (ORR) at the completion of combination therapy accessed by independent review committee (IRC) and investigator
Duration of Response (DOR) [Up to 3 years and 9 months]
Duration of Response (DOR) accessed by independent review committee (IRC) and investigator
Disease free survival (DFS) rate and event free survival (EFS) rate [Up to 2 years]
2-year disease free survival (DFS) rate and 2-year event free survival (EFS) rate
Overall survival (OS) rate [Up to 2 years]
2-year overall survival (OS) rate Accessed by independent review committee (IRC) and investigator
Occurrence of adverse events and serious adverse events according to CTCAE V5.0. [Up to 3 years and 9 months]
The safety of Orelabrutinib measured by the occurrence of adverse events and serious adverse events according to CTCAE V5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women between 18 and 80 years old
Histologically confirmed diffuse large B-cell lymphoma (DLBCL)
At least one measurable lesion by CT/MRI.
DLBCL with MCD subtype
Lymphoma International Prognostic Score (IPI) ≥ 2.
Ann Arbor stage II-IV, or stage I with bulky lesion (diameter > 7.5 cm）
ECOG PS score of 0-2
Subjects who in line with the testing standard of the clinical trial laboratory.
Life expectancy ≥ 6 months.
Able to provide signed written informed consent.

Exclusion Criteria:

History of other active malignancies within 5 years of study entry, unless cured without evidence of relapse or metastasis
Lymphoma involving the central nervous system or leptomeningeal metastasis.
Transformed lymphoma, that is transformed from other types of lymphoma.
Primary mediastinal large B-cell lymphoma.
History of stroke or intracranial hemorrhage within 6 months before screening.
Co-morbidity of uncontrolled or significant cardiovascular disease, significant impaired lung function, significant gastrointestinal abnormalities, uncontrolled infections (including HBV, HCV, HIV/AIDS and tuberculosis), or active autoimmune disease.
Active bleeding within 2 months before screening, or a clear bleeding tendency determined by the investigator; a history of deep vein thrombosis or pulmonary embolism.
Previous history of surgeries (major 4 weeks and minor 2 weeks prior screening) , organ transplant or hematopoietic stem cell transplantation, or progressive multifocal leukoencephalopathy (PML).
Administer live and attenuated vaccines (semi-inactivated) within 28 days prior to first receiving the test drug.
Planned stem cell transplant during the experimental treatment are excluded.
Prior corticosteroids (at dosages equivalent to prednisone > 20 mg/day) given with anti-neoplastic intent within 7 days, prior chemotherapy, targeted therapy, radiation therapy, or antibody-based therapies or anti-cancer TCM within 4 weeks of the start of study drug.
Current diagnosis of any mental or cognitive impairment, drug abuse, or alcohol abuse.
Pregnant, lactating women, or women at childbearing ages who will not use contraception during the study up to 12 months after the last dose of rituximab or 180 days after the last dose of study drug
The last use of CYP3A inhibitor or CYP3A inducer is less than 5 half-lives from the first trial drug, or the drug or food with moderate and strong CYP3A inhibitory effect or strong CYP3A induction effect is planned to be taken at the same time during this study.
Any serious medical condition that, in the investigator's opinion, would put the subject at unacceptable risk and/or would prevent the subject from signing the informed consent form. In the opinion of the investigator, the subject's participation in the study would be at unacceptable risk.