Linperlisib Plus Obinutuzumab and Venetoclax for Relapsed and Refractory Blastoid Variant of Mantle Cell Lymphoma.

NCT06324994 | Not Yet Recruiting Phase 2

• 1 other identifier: YY-20394-BV-MCL
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open label, national multicenter clinical study included patients with relapsed and refractory blastoid variant of mantle cell lymphoma (R/R BV-MCL), aiming to evaluate the efficacy of a chemotherapy free triple therapy of PI3K inhibitor (Linperlisib) combined with anti-CD20 monoclonal antibody (Obinutuzumab) and BCL-2 inhibitor (Venetoclax) in R/R BV-MCL patients.

Conditions

Mantle Cell Lymphoma

Keywords

Linperlisib; Venetoclax; Obinutuzumab

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) according to the RECIST 1.1

  The ORR rate of patients with Linperlisib in combination with Obinutuzumab and Venetoclax for relapsed and refractory blastoid variant of mantle cell lymphom

  At the end of Cycle 6 (each cycle is 28 days)

Secondary Outcomes (4)

• Progression-free survival (PFS)

  From date of enrollment until the date of first documented progression and loss of follow-up or date of death from any cause, whichever came first, assessed up to 24 months

• Overall survival (OS)

  From date of enrollment until the date of first date of death from any cause, expected evaluation period of up to 48 months

• Duration of Overall Response (DOR)

  From date of the time from the first assessment of the tumor as CR or PR to the first assessment as PD (Progressive Disease) or death from any cause,assessed up to 24 months

• Adverse event (AE)

  Record any adverse events starting from the first medication use until the end of the safety follow-up period. The evaluation period shall not exceed 24 months.

Study Arms (1)

cohort 1

EXPERIMENTAL

Patients with relapsed refractory lymphoblastic mantle cell lymphoma who have not previously received treatment with PI3K inhibitors and BCL-2 inhibitors

Drug: Linperlisib in combination with Obinutuzumab and Venetoclax

Interventions

Linperlisib in combination with Obinutuzumab and Venetoclax DRUG

Combined induction period: Linprixate: 80 mg, oral (pre - and post meal), once a day; Otuzumab: 1000 mg/dose, intravenous infusion, administered on the first day (1st cycle is 1, 8, 15 days); (Up to 6 cycles, administration cycle can be adjusted according to clinical treatment conditions); Vineclavone: increase from 40mg, 100mg, and 200mg to 400mg within 4 weeks, followed by a treatment cycle of 400mg orally once a day; (Starting from the third cycle), one cycle every 28 days, for a total of 6 cycles。 Maintenance treatment period: Linprixate: 80 mg, oral (both before and after meals), once a day; Vinecala: 400 mg, oral, once daily; Cycle every 28 days.

Also known as: Treatment group

cohort 1

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;
• Mother cell type mantle cell lymphoma (BV-MCL) confirmed by histopathological and immunophenotypic analysis;
• The Eastern Oncology Collaborative Group (ECOG) scored 0-2 on physical fitness status;
• Expected lifespan ≥ 3 months
• There is at least one measurable lesion: the longest diameter (LDi) of lymph node lesions is ≥ 1.5 cm, or the LDi of extralymph node lesions is ≥ 1 cm, or splenomegaly, or bone marrow involvement with or without malignant lymphocytosis;
• Have not received treatment with PI3K inhibitors and BCL-2 inhibitors in the past; Having sufficient bone marrow and organ functions;
• Having sufficient bone marrow and organ functions;
• All screening period laboratory tests must be conducted according to the requirements of the plan, and must be conducted within 7 days before enrollment. The values of laboratory tests conducted for screening must meet the following criteria:
• Blood routine examination (no blood transfusion, no use of granulocyte colony-stimulating factor (G-CSF), no medication correction within 14 days prior to screening):
• Hemoglobin (Hb) ≥ 80 g/L;
• Neutrophils (ANC) ≥ 1.0 × 109/L;
• Platelet count (PLT) ≥ 75 × 109/L;
• Biochemical examination:
• TBIL\<1.5 × Upper limit of normal range (ULN);
• Glutamate alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN;

You may not qualify if:

• Patients who have received any targeted PI3K or BCL treatment before enrollment;
• History of other primary invasive malignant tumors that have not been relieved or have not been relieved for more than 3 years;
• Those with involvement of the central nervous system (meninges or brain parenchyma);
• Individuals who are known to have allergies to any medication in the study;
• Participated in clinical trials of other drugs within 4 weeks prior to the start of the study;
• Pregnant or lactating women;
• Individuals with active infections, excluding fever related to tumor B symptoms;
• Concomitant diseases and medical history:
• There are multiple factors that affect oral medication, such as inability to swallow, chronic diarrhea, and intestinal obstruction
• Individuals with a history of psychiatric drug abuse who are unable to quit or have mental disorders;
• Subjects with any severe and/or uncontrolled diseases, including:
• Poor blood pressure control (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg);
• Suffering from ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia \[including QTc ≥ 450ms (male), QTc ≥ 470ms (female)\], and ≥ grade 2 congestive heart failure \[NYHA classification\];
• Active interstitial pneumonia or other chronic lung diseases leading to severe impairment of lung function, defined as FEV1 and DLCOc\<60% of normal predicted values;
• Liver abnormalities;

Sponsors & Collaborators

• Dalian Medical University: lead

Study Sites (1)

The Second Hospital Dalian Medical University

Dalian, Liaoning, 116000, China

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

obinutuzumab; venetoclax

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

Study Officials

• Xiuhua Sun, Doctor

  Dalian Medical University

  STUDY DIRECTOR

Central Study Contacts

Xiuhua Sun, Doctor

CONTACT

+86 17709873631; 3038668@vip.sina.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: Chief physician

Study Record Dates

• First Submitted: March 9, 2024
• First Posted: March 22, 2024
• Study Start: May 1, 2024
• Primary Completion: May 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)