Orelabrutinib in Combination with R-CHOP for CD5-positive DLBCL Patients（Rocket Trial）

Phase 2

Recruiting

Brief Summary: This is a prospective, single-arm, multicenter, phase II clinical trial to evaluate the efficacy and safety of orelabrutinib combined with the R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) regimen as first-line treatment in CD5-positive diffuse large B-cell lymphoma (DLBCL) patients.

Detailed Description: The purpose of this phase II clinical trial is to evaluate the efficacy and safety of orelabrutinib in combination with R-CHOP for untreated CD5-positive DLBCL patients.

The induction phase consisted of 6 cycles of orelabrutinib in combination with R-CHOP (orelabrutinib added from the second cycle), followed by 2 cycles of rituximab + orelabrutinib, for a total of 8 treatment cycles. After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with orelabrutinib will be conducted.

The primary endpoint is the 2-year event-free survival (EFS) rate.

Recruitment & Eligibility

Inclusion Criteria

Subjects fully understand and voluntarily participate in this study and sign informed consent.
Aged ≥18 years, both male and female.
Pathologically confirmed CD5-positive DLBCL
There must be at least one measurable or evaluable lesion that meets the evaluation criteria for Lugano 2014 lymphoma.
Eastern Cooperative Oncology Group(ECOG) performance status score of 0-2.
Expected survival ≥3 months.
Sufficient bone marrow, liver, and kidney function.

Key

Exclusion Criteria

DLBCL combined with other types of lymphoma. Transformed DLBCL.
DLBCL with central nervous system invasion.
The patients had previously received BTK inhibitors.
The patients have contraindications to any drug in the combined treatment.
Patients with the infection of human immunodeficiency virus (HIV) and/or acquired immunodeficiency syndrome.
Inability to swallow tablets, presence of malabsorption syndrome, or any other gastrointestinal disease or dysfunction that may affect the absorption of the study drug.
Pregnant and lactating women, and subjects of childbearing age who do not want to use contraception.
Mentally ill persons or persons unable to obtain informed consent.
The investigators think that the patient is not suitable for the study.

Arm && Interventions

Group	Intervention	Description
Orelabrutinib in combination with R-CHOP	Orelabrutinib Oral Tablet	Patients with CD5 positive diffuse large B-cell lymphoma will receive orelabrutinib in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle). After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with orelabrutinib will be conducted.
Orelabrutinib in combination with R-CHOP	R-CHOP Protocol	Patients with CD5 positive diffuse large B-cell lymphoma will receive orelabrutinib in combination with R-CHOP regimen from the second cycle of R-CHOP (3 weeks per cycle). After 8 cycles of induction therapy, if the response is assessed as complete remission (CR), maintenance therapy with orelabrutinib will be conducted.

Primary Outcome Measures

Name	Time	Method
2-year event-free survival (EFS) rate	Defined as the proportion of patients without disease progression, treatment discontinuation, or death for any reason within 24 months of enrollment	To investigate the preliminary anti-tumor efficacy

Secondary Outcome Measures

Name	Time	Method
Complete response rate (CRR)	Up to 8 cycles (each cycle is 21 days)	To investigate the preliminary anti-tumor efficacy
Disease-free survival (DFS)	From date of the first complete response until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months	To investigate the preliminary anti-tumor efficacy
Objective response rate (ORR)	Up to 8 cycles (each cycle is 21 days)	To investigate the preliminary anti-tumor efficacy
Progression-free survival (PFS)	From the date of enrollment until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months	To investigate the preliminary anti-tumor efficacy
Overall survival (OS)	From the date of enrollment until the date of death from ant cause, assessed up to 24 months	To investigate the preliminary anti-tumor efficacy
Number of participants with adverse events (AE) and severe adverse events (SAE) as assessed by CTCAE v5.0	Through study completion, an average of 2 years	To identify the incidence of AE and SAE

Locations (11): Gansu Cancer Hospital
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Lanzhou, Gansu, China
Dongguan People's Hospital
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Dongguan, Guangdong, China
Fifth Affiliated Hospital of Guangzhou Medical University
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Guangzhou, Guangdong, China
First People's Hospital of Guangzhou
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Guangzhou, Guangdong, China
Guangdong Provincial Hospital of Traditional Chinese Medicine
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Guangzhou, Guangdong, China
Second Affiliated Hospital of Guangzhou Medical University
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Guangzhou, Guangdong, China
First Affiliated Hospital of Shantou University Medical College.
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Shantou, Guangdong, China
Shenzhen People's Hospital
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Shenzhen, Guangdong, China
Zhaoqing First People's Hospital
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Zhaoqing, Guangdong, China
Fifth Affiliated Hospital of Sun Yat-sen University
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Zhuhai, Guangdong, China
Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen University,
🇨🇳
Guangzhou, China