Combination treatment for marginal zone lymphoma patients

A Single Arm, Open Center, Multicenter Clinical Study of Frontline Treatment of Marginal Zone Lymphoma Patients (MZL) With Linperlisib Combined With Obinutuzumab

This study is testing a new combination of two drugs, Linperlisib and obinutuzumab, to see if they can safely help patients with marginal zone lymphoma as their first treatment.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Hospital of Jilin University (Academic / other)
• Drugs / interventions: obinutuzumab
• Locations: 1 site (Changchun, Jilin)
• Trial ID: NCT06592170 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of a combination therapy using Linperlisib and obinutuzumab as a first-line treatment for patients with marginal zone lymphoma (MZL). It consists of a Phase Ib safety introduction stage to determine the recommended Phase II effective dose based on dose limiting toxicity, followed by a Phase II expansion phase involving induction therapy. Patients will receive Linperlisib at a determined dose combined with obinutuzumab, with ongoing treatment until disease progression or other reasons for discontinuation arise.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with newly diagnosed marginal zone lymphoma confirmed by histopathology.

Not a fit: Patients who have received previous anti-tumor treatments or have severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with marginal zone lymphoma.

How similar studies have performed: While this approach is novel, similar combination therapies have shown promise in treating other types of lymphoma.

Eligibility criteria

Inclusion Criteria:

* 1\. 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):

1. Hemoglobin (Hb) ≥ 90 g/L;
2. Neutrophil count (ANC) ≥ 1.5 × 10\*9/L;
3. Platelets (PLT) ≥ 100 × 10\*9/L;

Biochemical examination:

1. TBIL\<1.5 x upper limit of normal range (ULN);
2. Glutamate alanine aminotransferase (ALT) and Glutamate aspartate aminotransferase (AST) ≤ 2.5 × ULN;
3. Serum creatinine (Cr) ≤ 1.25 × ULN or Endogenous creatinine clearance rate ≥ 60 mL/min (Cockcroft Gault formula);

Coagulation function:

1. International Normalized Ratio (INR) ≤ 1.5 × ULN;
2. 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

Exclusion Criteria:

* 1\. 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:

  1. There are multiple factors that can affect oral medication, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
  2. Individuals with a history of abuse of psychotropic drugs who are unable to quit or have mental disorders;
  3. Subjects with any severe and/or uncontrolled illnesses, including:

     1. Poor blood pressure control (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 100 mmHg);
     2. Suffering from ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia \[including QTc ≥ 450ms (male), QTc ≥ 470ms (female)\], and ≥ grade 2 congestive heart failure \[New York Heart Association (NYHA) classification\];
     3. 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.
     4. Liver abnormalities:
     5. Decompensated cirrhosis (Child Pugh liver function rating B or C)
     6. Known history of liver disease with clinical significance. Including viral hepatitis, known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e. HBV DNA positive (\>2500 copies/mL or \>500IU/mL, and greater than the upper limit of normal); Known to be infected with hepatitis C virus (HCV) and HCV RNA positive (\>1 × 103 copies/mL). Note: hepatitis B HBsAg positive subjects who meet the inclusion conditions, whether their HBV DNA is measurable or not, need to continue antiviral treatment (nucleoside analogues are recommended) and regularly monitor HBV DNA; For subjects with positive HBcAb but negative HBsAg in hepatitis B, HBV DNA should be monitored regularly and preventive antiviral treatment should be recommended; HCV RNA should be regularly monitored in subjects with hepatitis C.
     7. Patients with renal failure requiring hemodialysis or peritoneal dialysis;
     8. Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites that require repeated drainage;
     9. Poor control of diabetes (FBG\>10mmol/L);
     10. 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.

Where this trial is running

Changchun, Jilin

• The First Hospital of Jilin University — Changchun, Jilin, China (Recruiting)

Study contacts

• Study coordinator: Ou Bai Ou Bai, MD/PHD, The First Hospital of Jilin University, MD/PHD

Conditions Lymphoma