Trial Title:
ZR2 Sequential Immunochemotherapy for Newly Treated MCL
NCT ID:
NCT05992597
Condition:
Rituximab, Lenalidomide, Zebutinib ，Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
ZR2 RDHAP
Description:
ZR2:Rituximab 375mg/m2, D1, Lenalidomide 24mg qd D1-14, zebutinib 160mg bid
RDHAP:Rituximab 375mg/m2 D0, dexamethasone 40mg D1-4, cytarabine 2g/m2 q12h D2, cisplatin
25mg/m2 D1-3.
Arm group label:
rituximab, lenalidomide, and zebutinib,RDHAP
Summary:
Patients with newly diagnosed MCL were treated with ZR2 regimen for 3 cycles, followed by
3 cycles of immunochemotherapy, and zebrutinib maintenance therapy for 2 years after the
end of induction therapy, in order to improve the remission rate and prognosis of
patients with induction therapy.
Detailed description:
This is a prospective, single-arm, multicenter, Phase II clinical study evaluating
sequential immunochemotherapy followed by rituximab, lenalidomide, and zebutinib combined
with or without autologous hematopoietic stem cell transplantation followed by zebutinib
maintenance therapy for initial treatment of capsular cell lymphoma. There are three
stages: screening, treatment and follow-up. The screening period was 28 days before the
first administration. Treatment period: Enrolled subjects first received 3 cycles of
rituximab, lenalidomide, zebutinib without chemotherapy (21 days for one cycle), followed
by 3 cycles of RDHAP immunochemotherapy (21 days for one cycle); All patients were
assessed with interim Positron Emission Tomography (iPET) after 3 cycles of rituximab,
lenalidomide, and zebutinib without chemotherapy. All patients will continue to receive 3
cycles Of RDHAP, followed by Treatment End Of Positron Emission Tomography. For patients
who have achieved complete metabolic response (CMR) or partial metabolic response (PMR),
autologous hematopoietic stem cell transplantation (ASCT) can be performed as
consolidation therapy after the researchers evaluate their physical status and their
personal wishes. 3 months after ASCT, PET will be reviewed for efficacy evaluation after
transplantation. Zebutinib maintenance therapy was started 2 months after transplantation
for 2 years. For patients without ASCT, zebutinib maintenance therapy was started
directly for 2 years. The follow-up period was entered after the end of maintenance
therapy. Efficacy was evaluated using Lugano2014 criteria. Patients with disease
progression during non-chemotherapy treatment were directly entered into RDHAP
immunochemotherapy, and patients with disease progression during immunochemotherapy were
directly removed from the group and entered second-line treatment. Objective effective
rate, safety index and survival data of patients were observed during the experiment.
Subjects will enter the follow-up period after the study treatment is discontinued or the
treatment period has been completed.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Participate in the clinical study voluntarily: fully understand and be informed of
the study and sign the informed consent in person; Willing to follow and be able to
complete all test procedures.
- 18~75 years old (inclusive), male and female.
- Histopathologically confirmed mantle cell lymphoma, including positive
immunohistochemical CyclinD1 (CyclinD1 or CCND1) and/or chromosomal t (11; 14) (q13;
Q32) ectopic.
- No prior anti-tumor therapy, such as chemotherapy, radiotherapy, immunotherapy or
biotherapy (tumor vaccine, cytokine, or growth factor controlling cancer).
- there must be at least one evaluable or measurable lesion that meets Lugano2014
criteria (evaluable lesion: PET/CT examination showing increased uptake in lymph
nodes or extratodal areas (higher than liver) and PET/CT and/or CT features
consistent with lymphoma; Measurable lesions: nodular lesions >15mm in length or
extragendal lesions >10mm in length with increased FDG uptake).
- Adequate organ and bone marrow function, no serious hematopoietic dysfunction,
abnormal heart, lung, liver, kidney function and immune deficiency (no blood
transfusion, granulocytic colony stimulating factor or other relevant medical
support within 14 days prior to the use of the study drug) :
A) Blood routine: neutrophil absolute count (ANC) ≥1.5×109/L (1500/mm3), platelet
≥75×109/L, hemoglobin ≥100g/L (if bone marrow is involved, platelet ≥50×109/L, ANC
≥1.0×109/L, hemoglobin ≥80g/L).
B) Liver function: serum bilirubin ≤2.5 times the upper limit of normal value, aspartate
aminotransferase (AST) and alanine aminotransferase (ALT)≤2.5 times the upper limit of
normal value (AST is allowed if liver is involved, ALT≤5 times the upper limit of normal
value).
C) Renal function: creatinine clearance ≥60 mL/min (estimated according to the
Cockcroft-Gault formula).
D) Coagulation function: INR≤1.5 times the upper limit of normal value; PT and APTT≤1.5
times the upper limit of normal value.
- Left ventricular ejection fraction (LVEF) ≥ 50% in cardiac function examination.
- Male subjects used effective contraception from signing informed consent until 6
months after the last chemotherapy.
- Life expectancy > 3 months.
Exclusion Criteria:
- The diagnosis was leukemic mantle cell lymphoma.
- Central nervous system involvement secondary to lymphoma.
- history of other active malignant diseases within 2 years prior to study entry, but
eligibility for inclusion :(1) adequately treated carcinoma in situ of the cervix;
(2) local basal cell carcinoma or squamous cell carcinoma of skin; (3) Pre-existing
malignant disease that is under control and has undergone local radical treatment
(surgical or other forms).
- People with a known history of Human Immunodeficiency Virus (HIV) infection and/or
acquired Immunodeficiency syndrome. Screening stage of hepatitis b surface antigen
or hepatitis c virus antibody positive patients, must further by hepatitis b virus
DNA (no more than 1000 iu/ml) and HCV RNA detection (shall not exceed the method
detection limit), in the activity of the ruled out the need for treatment after
hepatitis b or hepatitis c infection, before the experiment. Patients with hepatitis
B virus carriers, stabilized hepatitis B after drug treatment and cured hepatitis C
can be included.
- Major surgery was performed within 28 days prior to study initiation.
- Any active infections, including but not limited to bacterial, fungal or viral
infections, that require systemic antiinfective therapy within 14 days prior to
initiation of treatment.
- combined with severe or uncontrolled disease, including but not limited to
symptomatic of congestive heart failure, uncontrolled hypertension, unstable angina,
active peptic ulcer or A history of severe hemorrhagic diseases, such as hemophilia
a., hemophilia B, von willebrand disease or blood transfusion or other medical
intervention history of spontaneous bleeding.
- History of stroke or intracranial hemorrhage within 6 months prior to first
administration of the study drug.
- A history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the past
12 months.
- Patients who must take antiplatelet drugs and anticoagulant drugs at the same time
due to underlying diseases and have no alternative treatment plan.
- Continuous treatment with strong and moderate CYP3A inhibitors or CYP3A inducers is
required. Patients were excluded if they had taken a CYP3A potent or moderate-acting
inhibitor or inducer within 7 days prior to the first administration of the study
drug (or had taken these drugs for less than 5 half-lives).
- Patients deemed unsuitable for the study by other investigators.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Recruiting
Contact:
Last name:
Haiyan Yang, PhD
Phone:
0086-571-88122192
Email:
yanghy@zjcc.org.cn
Contact backup:
Last name:
Xi Chen, MD
Phone:
0086-571-88122192
Email:
zjuchenxi@126.com
Investigator:
Last name:
Xi Chen, MD
Email:
Sub-Investigator
Start date:
August 1, 2022
Completion date:
December 1, 2026
Lead sponsor:
Agency:
Zhejiang Cancer Hospital
Agency class:
Other
Source:
Zhejiang Cancer Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05992597
