IBI376 Plus Rituximab in Patients With Untreated Indolent Lymphoma.

NCT05073250 | Unknown Phase 2 DMC

• 1 other identifier: CHN-PLAGH-BT-068
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are the most common inert non Hodgkin's lymphoma (iNHL). The standard first-line treatment of advanced FL / MZL is based on rituximab. Whether combined with chemotherapy or not, iNHL can induce lasting remission, but most of it is usually incurable. Therefore, early treatment of advanced iNHL should focus on protecting the bone marrow function of patients. Although the first-line immunochemotherapy offer high efficacy but also high incidence of toxicity. Phosphatidylinositol 3-kinase (PI3K) pathway plays an important role in the occurrence and development of B-cell malignant tumors. Studies have shown that PI3K inhibitor alone has good antitumor effect and tolerance in patients with recurrent refractory iNHL. In addition, PI3K inhibitor combined with rituximab showed better prognosis compared with rituximab monotherapy in FL / MZL patients. Therefore, the chemo-free regime, PI3K inhibitor in combination with rituximab may explore a new avenue for FL and MZL patients.

Conditions

Inert Non Hodgkin's Lymphoma

Keywords

PI3K inhibitor; rituximab; follicular lymphoma; marginal zone lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete response (CR) rate

  The percentage of patients with CR was determined according to the revised lymphoma efficacy evaluation criteria (Lugano 2014 criteria).

  Within 6 months of induction therapy completion

Secondary Outcomes (4)

• Objective response rate (ORR)

  Within 6 months of induction therapy completion

• Duration of response (DOR)

  Within 6 months of induction therapy completion

• Progression-free survival（PFS）

  Within 6 months of induction therapy completion

• Safety of study treatments when given in combination

  Up to 90 days after the last dose of study drugs.

Other Outcomes (1)

• Biomarkers predictive of response

  Up to 12 months after the last dose of study drugs.

Study Arms (1)

Experimental arm

EXPERIMENTAL

Enrolled patients will be administered IBI376 plus rituximab, induction therapy for 6 cycles (28-day cycle). Patients assessed as partial response (PR) after 6 cycles of induction therapy will receive another 6 cycles of IBI376 combined with rituximab induction therapy.

Drug: IBI376; Biological: Rituximab

Interventions

IBI376 DRUG

IBI376 is administered orally once daily at a dose of 20 mg for 8 weeks, followed by an oral dose of 2.5 mg once daily. Patients assessed as PR after 6 cycles of induction therapy will receive another 6 cycles of IBI376 at an oral dose of 2.5 mg once daily.

Also known as: PI3Kδ inhibitor

Experimental arm

Rituximab BIOLOGICAL

Rituximab is administered at a dose of 375 mg/m\^2 intravenously in the first 4 weeks, once a week. Subsequently, rituximab will be dosed once every 4 weeks. Patients assessed as PR after 6 cycles of induction therapy will receive another 6 cycles of rituximab at a dose of 375 mg/m\^2 intravenously once every 4 weeks.

Also known as: Anti-cluster of differentiation antigen 20 (CD20) monoclonal antibody

Experimental arm

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 old, male or female;
• Grade 1-3a follicular lymphoma or marginal zone lymphoma derived from B cells was confirmed by pathology;
• Immunohistochemistry showed CD20 positive;
• Have not received systemic anti-tumor therapy in the past;
• Lugano stage is stage III-IV (Note: 2014 Lugano stage is adopted for non gastric or intranodal marginal zone lymphoma, and Lugano modified version of Ann Arbor stage system is adopted for gastrointestinal marginal zone lymphoma);
• Patients with Lugano stage I-II and recurrence only after radiotherapy can be included in the group;
• For subjects who relapsed only after radiotherapy, radiotherapy was completed 12 weeks before the first application of IBI376;
• Patients with Helicobacter pylori (HP) - positive mucosa associated lymphoid tissue lymphoma (MALT) can be enrolled if their pathological tissue type has not changed after failure of anti HP treatment;
• Any tumor load with treatment indications and one of the following is met:
• Have any discomfort symptoms that affect normal work and life;
• The function of end organs was impaired;
• Hemocytopenia secondary to lymphoma invading bone marrow;
• Massive lesions;
• Sustained or rapid progression
• The presence of evaluable target lesions is defined as the presence of ≥ 1 lesion with the longest diameter (LD) measurement \> 1.5cm and the longest vertical longitude (LPD) measurement ≥ 1.0cm assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Patients with splenic marginal zone lymphoma (SMZL) can be enrolled if there is no measurable target lesion, but there is a clear basis for lymphoma bone marrow infiltration (bone marrow smear, biopsy or flow cytometry);

You may not qualify if:

• Transformation from inert non-Hodgkin lymphoma to diffuse large B-cell lymphoma is known;
• Lymphoma involving the central nervous system;
• Known human immunodeficiency virus (HIV) infection or positive immunoassay;
• Viral infections that cannot be controlled by antiviral drugs, such as herpes virus infection, acute or chronic active hepatitis B, acute or chronic active hepatitis C, etc \[Note: chronic Hepatitis B virus (HBV) carriers or inactive hepatitis B surface antigen (HBsAg) positive subjects can be enrolled, and HBV-DNA is lower than the lower limit of detection; hepatitis C virus (HCV) antibody negative patients can be enrolled, HCV antibody positive patients need to be tested for HCV-RNA, and if they are negative, they can be enrolled\];
• There are active infectious diseases requiring treatment;
• Live vaccines were administered within 30 days before administration of the study drug;
• Active autoimmune diseases requiring systemic treatment in the past 12 months (i.e. the use of drugs to improve the disease, corticosteroids or immunosuppressive drugs). Note: alternative therapy (such as thyroxine, insulin or physiological corticosteroid replacement therapy with adrenal or pituitary insufficiency, etc.) is not considered as a systemic treatment;
• Known allergy or severe reaction to IBI376 or rituximab or any excipients;
• History of severe allergic reaction;
• There is congestive heart failure or uncontrolled arrhythmia classified as III-IV by the New York Heart Association;
• Patients with clinically significant electrocardiogram abnormalities and potential risk of malignant arrhythmia;
• Clinically significant heart diseases, including unstable angina pectoris, acute myocardial infarction and or heart problems, occurred within 6 months before study administration;
• A history of stroke or intracranial hemorrhage within 3 months before the date of administration of the study drug;
• Major surgery or severe trauma occurred within 28 days before the start of treatment, or major side effects have not recovered;
• Major uncontrolled medical conditions, including but not limited to kidney, liver, blood, gastrointestinal tract, endocrine, lung, nerve, brain or mental diseases;

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Biotherapeutic Department, Chinese PLA General Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone

Interventions

Rituximab; Antibodies, Monoclonal

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Weidong Han, Ph.D

  Biotherapeutic Department, Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weidong Han, Ph.D

CONTACT

+86-10-55499341; hanwdrsw@sina.com

Jinhong Shi, M.D

CONTACT

+86-10-66937231; jinhongshi321@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Biotherapeutic Department

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: October 11, 2021
• Study Start: December 31, 2021
• Primary Completion: December 31, 2023
• Study Completion: November 1, 2024
• Last Updated: May 12, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)