Trial Title:
Linperlisib Plus Obinutuzumab and Venetoclax for Relapsed and Refractory Blastoid Variant of Mantle Cell Lymphoma.
NCT ID:
NCT06324994
Condition:
Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Venetoclax
Obinutuzumab
Conditions: Keywords:
Linperlisib
Venetoclax
Obinutuzumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Linperlisib in combination with Obinutuzumab and Venetoclax
Description:
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.
Arm group label:
cohort 1
Other name:
Treatment group
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.
Detailed description:
This is a single arm, open label, national multicenter clinical study that included 10
cases of relapsed and refractory blastoid variant of mantle cell lymphoma (R/R BV-MCL).
The aim was to evaluate the efficacy of a chemotherapy free triple therapy consisting of
PI3K inhibitor (Linperlisib) combined with anti-CD20 monoclonal antibody (Obinutuzumab)
and BCL-2 inhibitor (Venetoclax) in patients with R/R BV-MCL. It is divided into a
combined induction period and a maintenance treatment period. All enrolled patients
receive the following combined treatment: combined induction period: Linperlisib: 80 mg,
orally (pre - and post meal), once a day; Obinutuzumab: 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);
Venetoclax: 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). Every 28
days, there are a total of 6 cycles. Maintenance treatment period: Linperlisib: 80 mg,
oral (both before and after meals), once a day; Venetoclax: 400 mg, oral, once daily.
Cycle every 28 days. After 6 cycles of combined treatment, the efficacy is evaluated
according to the Lugano2014 standard. If complete remission (CR) or partial remission
(PR) is achieved, maintenance treatment with a combination of 80 mg of linprixate and 400
mg of vinclair is administered every 28 days until disease progression, intolerable
toxicity, or other reasons lead to discontinuation. If it is stable disease (SD) and
progressive disease (PD), patients will be excluded from the group. The main research
endpoint is Objective Response Rate (ORR). Secondary study endpoints include progression
free survival (PFS); Overall survival (OS), duration of response (DOR), and safety:
incidence and severity of adverse events (AE) and severe adverse events (SAE). Safety:
incidence and severity of adverse events (AE) and severe adverse events (SAE).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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):
1. Hemoglobin (Hb) ≥ 80 g/L;
2. Neutrophils (ANC) ≥ 1.0 × 109/L;
3. Platelet count (PLT) ≥ 75 × 109/L;
Biochemical examination:
1. TBIL<1.5 × Upper limit of normal range (ULN);
2. Glutamate alanine aminotransferase (ALT) and 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 (unless the subject is receiving anticoagulant therapy and the
coagulation parameters (PT/INR and APTT) are within the expected range of anticoagulant
therapy at the time of screening):
1. International normalized ratio (INR) ≤ 1.5 × ULN;
2. Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
- Those who have not participated in clinical trials of other drugs within the 4
weeks prior to enrollment;
- Women with a possibility of pregnancy must undergo a serum pregnancy test
within 7 days before the first medication, and the result is negative. They are
willing to Intended to use efficient methods of contraception during the trial
period and within 1 year after the last administration of the investigational
drug. For male subjects whose partners are women of childbearing age, they
should undergo surgical sterilization or agree to use high-efficiency
contraception methods during the trial period and 1 year after the last
administration of the trial drug;
- The subjects voluntarily joined this study, signed an informed consent form,
had good compliance, and cooperated with follow-up.
Exclusion Criteria:
- 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:
1. There are multiple factors that affect oral medication, such as inability to
swallow, chronic diarrhea, and intestinal obstruction
2. Individuals with a history of psychiatric drug abuse who are unable to quit or
have mental disorders;
3. Subjects with any severe and/or uncontrolled diseases, including:
1. Poor blood pressure control (systolic blood pressure ≥ 150 mmHg 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 [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;
4. Liver abnormalities;
5. Decompensated cirrhosis (Child Pugh liver function rating of B or C)
6. Known clinically significant history of liver disease. Including viral
hepatitis, known carriers of hepatitis B virus (HBV) must exclude active
HBV infection, i.e. HBV DNA positivity (>2500 copies/mL or>500 IU/mL, and
above the upper limit of normal values); Known hepatitis C virus infection
(HCV) and HCV RNA positivity (>1×103copies/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; Hepatitis C patients need to regularly monitor HCV RNA.
7. 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>10 mmol/L);
10. Urine routine indicates urine protein ≥++, and it is confirmed that the
24-hour urine protein quantification is greater than 1.0 g;
- Have a history of immunodeficiency, including HIV testing positive, or other
acquired or congenital immunodeficiency diseases, or a history of organ
transplantation;
- According to the researcher's judgment, there are accompanying diseases that
seriously endanger patient safety or affect patient completion of the study. Unable
to understand the nature of the research or disagrees to sign an informed consent
form;
- The researcher evaluates other situations that are not suitable for inclusion in the
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
The Second Hospital Dalian Medical University
Address:
City:
Dalian
Zip:
116000
Country:
China
Contact:
Last name:
Xiuhua Sun, Doctor
Phone:
+86 17709873631
Email:
3038668@vip.sina.com
Start date:
May 1, 2024
Completion date:
December 1, 2026
Lead sponsor:
Agency:
Dalian Medical University
Agency class:
Other
Source:
Dalian Medical University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06324994