Orelabrutinib With R-CHOP-like Regimen for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

A Phase 2 Study of Orelabrutinib With R-CHOP-like Regimen for Patients With Newly Diagnosed Untreated Non-GCB DLBCL

The purpose of this study is to evaluate the efficacy and safety of orelabrutinib combined with rituximab，followed by orelabrutinib combined with R-CHOP-like regimen for newly diagnosed untreated Non-GCB DLBCL Patients

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: Orelabrutinib; Biological: Rituximab; Drug: CHOP-like Regimen

Detailed Description

The study will start with an initial 21-days of induction therapy with orelabrutinib and rituximab，following imaging examinations to evaluate response rates. Then treatment with 6 cycles chemoimmunotherapy (R-CHOP-like) either alone or in combination with orelabrutinib will depend on response during induction phase. Each cycle is 21 days.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • Recruiting
      • The First Affiliated Hospital of Soochow University
      • Contact: Zhengming Jin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed Non-GCB DLBCL
2. Age ≥18 and ≤75 years
3. At least one measurable lesion，measurable lymph nodes or masses of at least 15 millimeter (mm)
4. ECOG performance status 0-2
5. Lymphoma International Prognostic Score (IPI) ≥ 2
6. Life expectancy ≥ 6 months
7. Adequate organ and marrow function
8. Agreement to practice birth control from the time of enrollment until the follow-up period of the study

Exclusion Criteria:

1. Received major surgery within 4 weeks before treatment or existed unhealed wounds or ulcers, except biopsy related to lymphoma diagnosis
2. All patients with primary central nervous system lymphoma
3. History of stroke or intracranial hemorrhage within 6 months before screening, require or receive anticoagulant therapy with warfarin or an equivalent antagonist
4. Requires treatment with strong /moderate CYP3A inhibitors or inducers
5. Uncontrolled comorbidity or complications, including but not limited to: symptomatic congestive heart failure (New York Heart Association Class III-IV) or symptomatic or poorly controlled arrhythmias and/or significant pulmonary disease
6. HIV infection and/or active hepatitis B or active hepatitis C infection
7. Uncontrolled active systemic infection
8. Known hypersensitivity or contraindications to any drug involved in the study
9. Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Orelabrutinib+R-CHOP-like; Orelabrutinib plus Rituximab for 21 days; Following Imaging examinations, patients with ≥25% tumor reduction, treat with orelabrutinib 150mg qd orally plus R-CHOP-like for 6 cycles; whereas, patients with <25% tumor reduction, treat with R-CHOP-like alone for 6 cycle	Drug: Orelabrutinib; Orelabrutinib 150mg qd PO; Biological: Rituximab; Rituximab 375 mg/m2 IV on Day 1 of each 21-day cycle; Drug: CHOP-like Regimen; cyclophosphamide, anthracene nucleus chemotherapeutics（doxorubicin，liposomal doxorubicin）, vinca alkaloids（vincristine, vindesine），and glucocorticoid （dexamethasone，prednison）.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini response rate	The rate of patients who achieve ≥25% tumor reduction	the first 21 days
Complete Response Rate	The rate of patients who achieved complete response after treatment by OR-CHOP-like	At the end of Cycle 3 and Cycle 6（each cycle is 21 days）

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The rate of patients who achieved CR or PR after treatment by OR-CHOP-like	At the end of Cycle 3 and Cycle 6（each cycle is 21 days）
Progression-free survival（PFS）	PFS will be assessed from the first OR(Orelabrutinib plus Rituximab) given to date of progression, relapse, death or end of follow-up	up to 18 month after the last patient's enrollment
Incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events	The safety and tolerability of the therapeutic regimen measured by the incidence of Treatment-Emergent Adverse Events, Treatment-Related Adverse Events and Serious Adverse Events	initiation of study drug until 30 days after last dose

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 10, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Actual): August 12, 2022
• Last Update Submitted That Met QC Criteria: August 10, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Orelabrutinib
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: Jinzm 002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All the data would be available at the First Affiliated Hospital and other researchers after the end of the study
• IPD Sharing Time Frame: after the end of the study
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No