Linperlisib Combined With Immunochemotherapy in Relapsed/Refractory LBCL

NCT06489808 | Recruiting Phase 2

• 1 other identifier: IIT2024030
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of Linperlisib combined with standard immunochemotherapy in patients with R/R LBCL.

Conditions

Relapsed/Refractory Large B-Cell Lymphoma

Keywords

Linperlisib; Immunochemotherapy

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicities

  Dose-Limiting Toxicities per study protocol defination

  Safety Run-in Period, up to the end of cycle 1 (each cycle is 21 days)

• ORR

  Response is assessed according to the Lugano criteria

  up to 2 years

Secondary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events

  up to 2 years

• Complete Response Rate (CRR)

  up to 2 years

• Duration of Response (DOR)

  up to 2 years

• Duration of Complete Response (DOCR)

  up to 2 years

• Progression-free Survival (PFS)

  up to 2 years

Study Arms (2)

Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen

EXPERIMENTAL

Cohort 1 consisted of transplant-ineligible patients who received Linperlisib in combination with R-Gemox. The treatment regimen was as follows: Linperlisib (RP2D dosage) on Days 1-14, rituximab 375 mg/m² on Day 0, gemcitabine 1000 mg/m² on Day 1, and oxaliplatin 130 mg/m² on Day 1, every 21 days for 6 cycles.

Drug: Linperlisib; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

EXPERIMENTAL

Cohort 2 consisted of patients scheduled for transplantation who received 3 cycles of Linperlisib (RP2D, D1-14) combined with R-ICE/DHAP/GVM regimen (R-ICE regimen: rituximab, ifosfamide, carboplatin, etoposide; R-DHAP regimen: rituximab, cytarabine, dexamethasone, cisplatin; R-GVM regimen: rituximab, gemcitabine, vinorelbine, mitoxantrone liposome), followed by autologous hematopoietic stem cell transplantation in responding patients.

Drug: Linperlisib; Drug: Rituximab; Drug: Gemcitabine; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide; Drug: Dexamethasone; Drug: Cisplatin; Drug: Ara-C; Drug: Vinorelbine; Drug: Mitoxantrone hydrochloride liposome

Interventions

Linperlisib DRUG

Linperlisib RP2D D1-14

Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen; Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Rituximab DRUG

rituximab 375 mg/m2 D0

Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen; Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Gemcitabine DRUG

gemcitabine per regimen dosage

Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen; Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Oxaliplatin DRUG

Oxaliplatin 130 mg/m2 D1

Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen

Ifosfamide DRUG

Ifosfamide 5g/m2 D2

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Carboplatin DRUG

Carboplatin AUC=5mg/mL · min (maximum absolute dose/cycle = 800 mg)

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Etoposide DRUG

Etoposide 100mg/m2 D1-3

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Dexamethasone DRUG

Dexamethasone 40mg D1-4

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Cisplatin DRUG

Cisplatin 100mg/m2 D1, continuous intravenous infusion

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Ara-C DRUG

Ara-C 2g/m2 q12h D2

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Vinorelbine DRUG

Vinorelbine 20mg/m2 D1

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Mitoxantrone hydrochloride liposome DRUG

Mitoxantrone hydrochloride liposome 18mg/m2 D1

Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma unspecified (DLBCL, NOS), follicular lymphoma grade 3B (FL, 3B), high-grade B-cell lymphoma unspecified (HGBCL, NOS), DLBCL/HGBCL with MYC and BCL2 rearrangements, FL transformed DLBCL without a previous history of indolent lymphoma.
• Relapsed or refractory after first-line immunochemotherapy (which must include CD20 monoclonal antibody and anthracycline) 1)Refractory is defined as failure to achieve a complete response to first-line therapy (excluding patients who are intolerant to first-line therapy), including progressive disease (PD) as the best response to first-line therapy; stable disease (SD) as the best response after at least 4 cycles of first-line therapy (eg, 4 cycles of R-CHOP); partial response (PR) as the best response after at least 6 cycles of first-line therapy with biopsy-confirmed residual disease or disease progression within 12 months of initiating first-line therapy; complete response to first-line therapy followed by progression within 12 months after the end of therapy. 2)Relapse was defined as a complete response to first-line therapy followed by progression confirmed more than 12 months after the end of therapy.
• Subjects must have at least 1 measurable lesion/evaluable lesion that meets the 2014 version of the Lugano Lymphoma Evaluation Criteria.
• Subjects has no known or suspected central nervous system involvement by lymphoma.
• Previous treatment with any antineoplastic therapy (including radiation therapy, chemotherapy, hormonal therapy, surgery, or molecular targeted therapy) for which participation in this trial must have exceeded 2 weeks or 5 drug half-lives, whichever is shorter.
• Age ≥ 18 years.
• ECOG score 0-2.
• Expected survival ≥ 3 months.
• Women of Childbearing Potential subjects must have a negative serum/urine pregnancy test within 7 days prior to the first dose; female subjects of childbearing potential and male subjects with partners of childbearing potential, as well as their partners, should agree to use effective contraception from signing the ICF until 6 months after the last dose of study drug.
• Able to comply with the trial protocol as judged by the investigator.
• Each subject (or legally acceptable representative) voluntarily joined the study and signed an informed consent form.

You may not qualify if:

• Other malignancies within the last 5 years, except radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the breast, and carcinoma in situ of the cervix.
• Previous autologous or allogeneic hematopoietic stem cell transplantation.
• History of Richter transformation.
• Received \> 1 line of systemic antineoplastic therapy.
• Prior treatment with PI3K inhibitors.
• Known hypersensitivity to trial products.
• Active viral, bacterial, or fungal infection requiring treatment (eg, pneumonia, etc.).
• Requiring prolonged systemic hormones (at doses equivalent to \> 10 mg prednisone/day) or any other form of immunosuppressive therapy. Subjects taking inhaled or topical corticosteroids may be enrolled.
• Concomitant diseases and medical history:
• Multiple factors affecting oral medication (e.g. inability to swallow, chronic diarrhea, ileus, etc.).
• Patients with a history of psychotropic substance abuse who cannot quit or have mental disorders.
• Subjects with any severe and/or uncontrolled disease including:
• )Unsatisfactory blood pressure control (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg). 2)Patients with ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia (including QTc ≥ 450 ms (male), QTc ≥ 470 ms (female)) and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification). 3)Active interstitial pneumonia or other chronic lung disease resulting in severely impaired lung function defined as FEV1 and DLCOc \< 60% of predicted normal; history of interstitial pneumonia due to COVID-19. 4)Abnormal liver: I.Decompensated cirrhosis (Child-Pugh class B or C). II.Known history of clinically significant liver disease. 5)Renal failure requiring hemodialysis or peritoneal dialysis. 6)Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. 7)Urine routine showed urine protein ≥ + +, and confirmed 24-hour urine protein quantification \> 1.0 g.
• Patients with active or history of autoimmune diseases that may relapse (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulonephritis, etc.), or patients at high risk. Patients with autoimmune hypothyroidism requiring only hormone replacement therapy may be considered for enrollment if the disease is stable as assessed by the investigator.
• Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Disease Hospital

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

MeSH Terms

Conditions

Recurrence

Interventions

Rituximab; Gemcitabine; Oxaliplatin; Ifosfamide; Carboplatin; Etoposide; Dexamethasone; Cisplatin; Cytarabine; Vinorelbine

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Oxazines; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Lugui Qiu

  Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wei Liu, MD

CONTACT

+86 022-23608463; liuwei@ihcams.ac.cn

Lugui Qiu, MD

CONTACT

+86 022-23908461; qiulg@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2024
• First Posted: July 8, 2024
• Study Start: May 28, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: July 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)