Orelabrutinib, Rituximab and Combination Chemotherapy in Newly-diagnosed Aggressive B-cell Non-Hodgkin Lymphoma

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

B-cell non-Hodgkin's lymphoma (B-NHL) is the most common type of NHL. Although novel immunotherapies represented by anti-CD20 monoclonal antibodies and CAR-T cell therapies have significantly improved the prognosis of B-NHL patients, there are still nearly one-third of patients who are resistant to initial treatment or relapse after remission. R-CHOP combined with novel drugs was expected to improve the prognosis. Therefore, this study aimed to investigate the potential of R-CHOP combined with Orelabrutinib.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shandong Provincial Hospital
• Treatments: Cyclophosphamide; Doxorubicin; Etoposide; Prednisone; Rituximab; Vincristine

Criteria

Inclusion Criteria:

1. Age ≥18 years, gender not limited

2. Newly and histologically diagnosed aggressive B-NHL

3. Patients who have not received systematic chemotherapy or immunotherapy;

4. Patients with at least ≥1 tumor foci with a measurable maximum axis exceeding 1.5 cm;

5. Eastern cancer collaboration group(ECOG) physical status score: 0-2

6. Major organ functions meet the following criteria:

1. Blood routine: (independent of growth factor support or transfusion within 7 days of study entry) neutrophils absolute value ≥1.5×109/L, platelets ≥75×109/L,

2. Coagulation function：INR and APTT ≤2.5 times ULN，

3. Blood biochemistry：total bilirubin ≤2 times ULN, AST or ALT≤2.5 times ULN;

4. Renal function: Ccr ≥ 50 mL/min, total bilirubin, AST or ALT≤2.5 times ULN

7. Willing to take contraceptive measures during the trial period and within 3 months after the trial ends；

8. Voluntarily sign written informed consent before screening.

Exclusion Criteria:

1. Current or previous malignancy, unless radical therapy has been performed and there is no evidence of recurrence or metastasis in the past 5 years；

2. Patients scheduled for major surgery(examination for diagnostic purposes) within 4 weeks or participating in drug/device clinical trials;

3. Prior or concurrent indolent B-cell lymphoma transformation;

4. Have uncontrolled or significant cardiovascular disease, including:

1. New York Heart Association (NYHA) Grade II or higher congestive heart failure, unstable angina, and myocardial infarction occurred within 6 months before the first administration of the study drug or arrhythmia needing treatment at the time of screening, LVEF <50%；

2. Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy)；

3. Clinically significant QTc interval prolongation history, or QTc interval >470ms for female and >450ms for male in the screening period；

4. Symptomatic coronary heart disease patients or needing treatment;

5. Uncontrolled high blood pressure (on the basis of improving lifestyle, substandard blood pressure with reasonable and tolerable application of 2 or more antihypertensive drugs including diuretics for more than 1 month, or taking 4 or more antihypertensive drugs to control blood pressure effectively)；

5. Had active bleeding within 2 months prior to screening, or was taking anticoagulant drugs, or was considered by the investigator to have a clear tendency to bleeding;

6. Stroke or intracranial hemorrhage within 6 months；

7. Subjects with clinically significant gastrointestinal abnormalities that may affect drug intake, transport or absorption (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.);

8. Active or uncontrolled HBV (HBsAg positive and HBV DNA titer positive), HCV Ab positive or HIV positive；

9. Uncontrolled, active systemic fungal, bacterial, viral, or other infections (defined as showing persistent signs/symptoms related to infection, despite the use of appropriate antibiotics or other treatments without improvement)；

10. Allergies or hypersensitivity reactions to orelabrutinib, rituximab or any other component of the applicable study drug;

11. Combined with drugs with moderate to severe inhibitory effect or strong induction effect on CYP3A;

12. Severe mental illness;

13. Expected survival <6 months

14. Pregnant and lactating women; For women of childbearing age who do not agree to use appropriate methods of contraception;

15. Poor compliance or inability to visit regularly;

16. Potentially life-threatening patients, or severe organ dysfunction, judged unsuitable for this trail by investigators.