Trial Title:
Linperlisib Combined With Immunochemotherapy in Relapsed/Refractory LBCL
NCT ID:
NCT06489808
Condition:
Relapsed/Refractory Large B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Dexamethasone
Rituximab
Carboplatin
Gemcitabine
Oxaliplatin
Etoposide
Vinorelbine
Ifosfamide
Mitoxantrone
Conditions: Keywords:
Linperlisib
Immunochemotherapy
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Linperlisib
Description:
Linperlisib RP2D D1-14
Arm group label:
Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Rituximab
Description:
rituximab 375 mg/m2 D0
Arm group label:
Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
gemcitabine per regimen dosage
Arm group label:
Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Oxaliplatin
Description:
Oxaliplatin 130 mg/m2 D1
Arm group label:
Cohort 1 transplant-ineligible patients: Linperlisib combined with R-Gemox regimen
Intervention type:
Drug
Intervention name:
Ifosfamide
Description:
Ifosfamide 5g/m2 D2
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Carboplatin AUC=5mg/mL · min (maximum absolute dose/cycle = 800 mg)
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Etoposide 100mg/m2 D1-3
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Dexamethasone 40mg D1-4
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Cisplatin 100mg/m2 D1, continuous intravenous infusion
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Ara-C
Description:
Ara-C 2g/m2 q12h D2
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Vinorelbine
Description:
Vinorelbine 20mg/m2 D1
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Intervention type:
Drug
Intervention name:
Mitoxantrone hydrochloride liposome
Description:
Mitoxantrone hydrochloride liposome 18mg/m2 D1
Arm group label:
Cohort 2 patients scheduled for transplantation:Linperlisib combined with R-ICE/DHAP/GVM regimens
Summary:
To evaluate the efficacy and safety of Linperlisib combined with standard
immunochemotherapy in patients with R/R LBCL.
Detailed description:
This is a phase 2, open-label, multicenter, multi-cohort study evaluating the efficacy
and safety of Linperlisib combined with standard immunochemotherapy in the treatment of
relapsed/refractory LBCL after first-line treatment. This study is divided into a safety
run-in phase and a dose expansion phase.The primary objective of the safety run-in phase
was to determine the recommended dose for the dose expansion phase based on dose-limiting
toxicities (DLTs).
The dose expansion phase consisted of Cohort 1 and Cohort 2.Cohort 1 was
transplant-ineligible patients who received Linperlisib in combination with R-Gemox at
RP2D for 6 cycles.Cohort 2 consisted of patients scheduled for transplantation who
received 3 cycles of Linperlisib combined with R-ICE/DHAP/GVM regimen, followed by
autologous hematopoietic stem cell transplantation in responding patients
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. 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.
2. 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.
3. Subjects must have at least 1 measurable lesion/evaluable lesion that meets the 2014
version of the Lugano Lymphoma Evaluation Criteria.
4. Subjects has no known or suspected central nervous system involvement by lymphoma.
5. 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.
6. Age ≥ 18 years.
7. ECOG score 0-2.
8. Expected survival ≥ 3 months.
9. 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.
10. Able to comply with the trial protocol as judged by the investigator.
11. Each subject (or legally acceptable representative) voluntarily joined the study and
signed an informed consent form.
- Exclusion Criteria:
1. 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.
2. Previous autologous or allogeneic hematopoietic stem cell transplantation.
3. History of Richter transformation.
4. Received > 1 line of systemic antineoplastic therapy.
5. Prior treatment with PI3K inhibitors.
6. Known hypersensitivity to trial products.
7. Active viral, bacterial, or fungal infection requiring treatment (eg, pneumonia,
etc.).
8. 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.
9. Concomitant diseases and medical history:
1. Multiple factors affecting oral medication (e.g. inability to swallow, chronic
diarrhea, ileus, etc.).
2. Patients with a history of psychotropic substance abuse who cannot quit or have
mental disorders.
3. Subjects with any severe and/or uncontrolled disease including:
1)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.
4. 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.
10. Known history of human immunodeficiency virus (HIV) infection and/or acquired
immunodeficiency syndrome.
11. Positive pregnancy test at baseline in female patients who are pregnant, lactating,
or of childbearing potential.
12. Concurrent medical conditions that, in the investigator 's judgment, would seriously
compromise the patient' s safety or the patient 's completion of the study.
-
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institute of Hematology & Blood Disease Hospital
Address:
City:
Tianjin
Zip:
300020
Country:
China
Status:
Recruiting
Contact:
Last name:
Wei Liu, MD
Phone:
86-022-23908463
Email:
liuwei@ihcams.ac.cn
Investigator:
Last name:
Wei Liu, MD
Email:
Principal Investigator
Start date:
May 28, 2024
Completion date:
May 31, 2027
Lead sponsor:
Agency:
Institute of Hematology & Blood Diseases Hospital, China
Agency class:
Other
Source:
Institute of Hematology & Blood Diseases Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06489808
