Linperlisib Combination With Obinutuzumab Frontline Treatment of Marginal Zone Lymphoma Patients (MZL)

NCT06592170 | Recruiting Phase 1

• 1 other identifier: YY-20394-MZL-001
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open label, national multicenter clinical study included patients with marginal zone lymphoma patients (MZL) , aim is to evaluate the efficacy and safety of first-line treatment with Linperlisib combined with obinutuzumab in patients with marginal zone lymphoma (MZL).

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete response（CR） according to the RECIST 1.1

  The CR rate of patients with Linperlisib in combination with Obinutuzumab for marginal zone lymphoma

  6 months from the start of linperlisib treatment

Secondary Outcomes (5)

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

  6 months from the start of linperlisib treatment

• Duration of Overall Response (DOR）

  Within 2 year from the start of Linperlisib treatment，the time from the first judgment of complete remission (CR) or partial remission (PR) to the discovery of disease progression (PD)

• Adverse event

  Within 2 year from the start of Linperlisib treatment

• Disease control rate（DCR）

  Within 2 year from the start of Linperlisib treatment

• Progression-free survival（PFS）

  Within 2 years of initiation of Linperlisib treatment

Study Arms (1)

Experimental group

EXPERIMENTAL

Safe import period: Linperlisib: 80 mg, oral (pre - and post meal), QD; obinutuzumab: 1000 mg, intravenous infusion, administered on the first day (1st cycle on days 1, 8, and 15); Every 28 days, there is one cycle in total. Extended treatment period: Combination induction: Linperlisib: RP2D, oral (pre - and post meal), QD; obinutuzumab: 1000 mg/time, intravenous infusion, administered on the first day (1st cycle on days 1, 8, and 15); Every 28 days, there are 2 cycles in total. Afterwards, single drug maintenance: Linperlisib: RP2D, oral (before and after meals), QD; every 28 days per cycle.

Drug: Linperlisib combination with obinutuzumab

Interventions

Linperlisib combination with obinutuzumab DRUG

Safe import period: Linperlisib: 80 mg, oral (pre - and post meal), QD; obinutuzumab: 1000 mg, intravenous infusion, administered on the first day (1st cycle on days 1, 8, and 15); Every 28 days, there is one cycle in total. Extended treatment period: Combination induction: Linperlisib: RP2D, oral (pre - and post meal), QD; obinutuzumab: 1000 mg/time, intravenous infusion, administered on the first day (1st cycle on days 1, 8, and 15); Every 28 days, there are 2 cycles in total. Afterwards, single drug maintenance: Linperlisib: RP2D, oral (before and after meals), QD; every 28 days per cycle.

Experimental group

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, both male and female are acceptable; 2. Newly diagnosed marginal zone lymphoma confirmed by histopathology. Including extranodal MZL, intranodal MZL, and splenic MZL; 3. There is at least one measurable lesion: the longest diameter (LDi) of a lymph node lesion is greater than 1.5 cm or the LDi of an extra lymph node lesion is greater than 1 cm (according to the 2014 Lugano classification); 4. The physical status score of the Eastern Cooperative Oncology Group (ECOG) is ≤ 2; 5. Expected lifespan ≥ 12 weeks; 6. Have not received any previous anti-tumor treatment; 7. Possess sufficient bone marrow and organ functions; 8. All screening laboratory tests must be conducted according to the protocol requirements, and must be conducted within 7 days prior to enrollment. The values of laboratory tests conducted for screening must meet the following standards:
• Blood routine examination (no blood transfusion within 14 days before screening, no use of granulocyte colony-stimulating factor (G-CSF), no medication correction):
• Hemoglobin (Hb) ≥ 90 g/L;
• Neutrophil count (ANC) ≥ 1.5 × 10\*9/L;
• Platelets (PLT) ≥ 100 × 10\*9/L;
• Biochemical examination:
• TBIL\<1.5 x upper limit of normal range (ULN);
• Glutamate alanine aminotransferase (ALT) and Glutamate aspartate aminotransferase (AST) ≤ 2.5 × ULN;
• Serum creatinine (Cr) ≤ 1.25 × ULN or Endogenous creatinine clearance rate ≥ 60 mL/min (Cockcroft Gault formula);
• Coagulation function:
• International Normalized Ratio (INR) ≤ 1.5 × ULN;
• Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; 9. Women who have the possibility of pregnancy must undergo a serum pregnancy test within 7 days before the first use of the test drug, and the result must be negative. They must also be willing to use effective contraception methods during the trial period and within 1 year after the last administration of the test drug. For male participants whose partners are women of childbearing age, surgical sterilization should be performed, or they should agree to use efficient contraception methods during the trial period and one year after the last administration of the trial drug; 10. The subjects voluntarily joined this study, signed an informed consent form, had good compliance, and cooperated with follow-up

You may not qualify if:

• \. Patients who have received any targeted PI3K therapy before enrollment; 2. History of other primary invasive malignant tumors that have not been relieved or have not been relieved for more than 3 years; 3. Patients with involvement of the central nervous system (meninges or brain parenchyma); 4. Individuals who are known to have allergies to any of the drugs in the study; 5. Participated in clinical trials of other drugs within 4 weeks prior to the start of the study; 6. Pregnant or lactating women; 7. Individuals with active infections, except for those with tumor related B symptoms and fever; 8. Combined diseases and medical history:
• There are multiple factors that can affect oral medication, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
• Individuals with a history of abuse of psychotropic drugs who are unable to quit or have mental disorders;
• Subjects with any severe and/or uncontrolled illnesses, including:
• Poor blood pressure control (systolic blood pressure ≥ 150mmHg 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 \[New York Heart Association (NYHA) classification\];
• 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; History of interstitial pneumonia caused by COVID-19.
• Liver abnormalities:
• Decompensated cirrhosis (Child Pugh liver function rating B or C)
• Patients with renal failure requiring hemodialysis or peritoneal dialysis;
• Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites that require repeated drainage;
• Poor control of diabetes (FBG\>10mmol/L);
• Urine routine shows urinary protein ≥++and confirms 24-hour urinary protein quantification\>1.0g; 9. History of immunodeficiency, including HIV testing positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; 10.According to the researchers assessment, there are accompanying diseases that pose a serious threat to patient safety or affect the completion of the study.

Sponsors & Collaborators

• The First Hospital of Jilin University: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, 130000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma

Interventions

obinutuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Ou Bai Ou Bai, MD/PHD, The First Hospital of Jilin University, MD/PHD

CONTACT

13039046656; oubai16@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: September 7, 2024
• First Posted: September 19, 2024
• Study Start: August 13, 2024
• Primary Completion: August 13, 2025
• Study Completion (Estimated): August 13, 2027
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)