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

NCT05097443 | Unknown Phase 3

• 1 other identifier: B-NHL001
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief 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 Orelabrutinib combined with Rituximab and chemotherapy.

Conditions

High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements; High Grade B-Cell Lymphoma, Not Otherwise Specified; Diffuse Large B-cell Lymphoma; Mantle Cell Lymphoma; B-cell NonHodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• ORR

  At the end of Cycle 6 (each cycle is 21 days)

Secondary Outcomes (3)

• Occurrence of adverse events and serious adverse events

  3 years

• progression-free survival (PFS)

  3 years

• Overall survival (OS)

  3 years

Study Arms (1)

Orelabrutinib+R+chemotherapy

EXPERIMENTAL

Orelabrutinib+R-CHOP;Orelabrutinib+R-DA-EPOCH;Orelabrutinib+R-HD MTX；Orelabrutinib+R+other regimens

Drug: Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapies

Interventions

Orelabrutinib+R-CHOP; Orelabrutinib+R-DA-EPOCH; Orelabrutinib+R-HD MTX;Orelabrutinib+R+other chemotherapies DRUG

Orelabrutinib+R-CHOP： Orelabrutinib 150mg qd; R-CHOP：Rituximab 375mg/m2 d0, Cyclophosphamide 750mg /m2 d1, Doxorubicin 50mg /m2 or Doxorubicin liposome 30-40 mg /m2 d1, Vincristine 1.4mg /m2 or Vindesine 3mg /m2 d1, Prednisone 100mg d1-5. Orelabrutinib+R-DA-EPOCH： Orelabrutinib 150mg qd； R-DA-EPOCH：Rituximab 375mg/m2 d0, Etoposide 50mg/ m2, Epirubicin 15mg/ m2, Vincristine 0.4mg/ m2, d1-4, Cyclophosphamide 750mg/ m2 d5, Prednisone 60mg/ m2 d1-5. Orelabrutinib+R-HD-MTX: Orelabrutinib 150mg qd; R-HD-MTX: Rituximab 375mg/m2 d0, Methotrexate 3.5g/ｍ2 d1. Orelabrutinib+ R+other regimens: Orelabrutinib 150mg qd； R+other regimens: Rituximab 375mg/m2 d0. The dose of other drugs depends on the regimen. All regimens follow every 21 days is one cycle, which can be extended to 28 days per cycle according to patients' specific tolerance. Dose adjustments of Orelabrutinib are allowed. The initial dose is 150 mg, QD, while the first adjustment is 100 mg, QD and the second adjustment is 50 mg, QD.

Orelabrutinib+R+chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years, gender not limited
• Newly and histologically diagnosed aggressive B-NHL
• Patients who have not received systematic chemotherapy or immunotherapy;
• Patients with at least ≥1 tumor foci with a measurable maximum axis exceeding 1.5 cm;
• Eastern cancer collaboration group(ECOG) physical status score: 0-2
• Major organ functions meet the following criteria:
• 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,
• Coagulation function：INR and APTT ≤2.5 times ULN，
• Blood biochemistry：total bilirubin ≤2 times ULN, AST or ALT≤2.5 times ULN;
• Renal function: Ccr ≥ 50 mL/min, total bilirubin, AST or ALT≤2.5 times ULN
• Willing to take contraceptive measures during the trial period and within 3 months after the trial ends；
• Voluntarily sign written informed consent before screening.

You may not qualify if:

• Current or previous malignancy, unless radical therapy has been performed and there is no evidence of recurrence or metastasis in the past 5 years；
• Patients scheduled for major surgery(examination for diagnostic purposes) within 4 weeks or participating in drug/device clinical trials;
• Prior or concurrent indolent B-cell lymphoma transformation;
• Have uncontrolled or significant cardiovascular disease, including:
• 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%；
• Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmic right ventricular cardiomyopathy, restrictive cardiomyopathy, indeterminate cardiomyopathy)；
• Clinically significant QTc interval prolongation history, or QTc interval \>470ms for female and \>450ms for male in the screening period；
• Symptomatic coronary heart disease patients or needing treatment;
• 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)；
• 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;
• Stroke or intracranial hemorrhage within 6 months；
• Subjects with clinically significant gastrointestinal abnormalities that may affect drug intake, transport or absorption (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
• Active or uncontrolled HBV (HBsAg positive and HBV DNA titer positive), HCV Ab positive or HIV positive；
• 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)；
• Allergies or hypersensitivity reactions to orelabrutinib, rituximab or any other component of the applicable study drug;

Sponsors & Collaborators

• Shandong Provincial Hospital: lead

Study Sites (1)

Shandong Provincial Hospital

Jinan, Shandong, 250021, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Xin Wang, PhD

  Shandong Provincial Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xin Wang, PhD

CONTACT

86-531-13156012606; xinw@sdu.edu.cn

Xiangxiang Zhou, PhD

CONTACT

86-531-15866695595; xiangxiangzhou@sdu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Department of Hematology

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: October 28, 2021
• Study Start: April 15, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: November 19, 2021

Record last verified: 2021-11

Locations

CN (1)