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ZR2 Sequential Immunochemotherapy for Newly Treated MCL

Primary Purpose

Rituximab, Lenalidomide, Zebutinib ,Mantle Cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
ZR2 RDHAP
Sponsored by
Zhejiang Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rituximab, Lenalidomide, Zebutinib ,Mantle Cell Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Zhejiang Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

rituximab, lenalidomide, and zebutinib,RDHAP

Arm Description

Outcomes

Primary Outcome Measures

ORR
overall response rate

Secondary Outcome Measures

PFS
Progression Free Survival
OS
Overall Survival
AE and SAE
Adverse event and serious adverse event

Full Information

First Posted
August 8, 2023
Last Updated
September 17, 2023
Sponsor
Zhejiang Cancer Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05992597
Brief Title
ZR2 Sequential Immunochemotherapy for Newly Treated MCL
Official Title
Prospective, Single-arm, Single-center, Phase II Clinical Study of Rituximab, Lenalidomide, Zebutinib Combined Regimen Followed by Sequential Immunochemotherapy in the Treatment of Initially Treated Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2022 (Actual)
Primary Completion Date
August 1, 2025 (Anticipated)
Study Completion Date
December 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang Cancer Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rituximab, Lenalidomide, Zebutinib ,Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
rituximab, lenalidomide, and zebutinib,RDHAP
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ZR2 RDHAP
Intervention 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.
Primary Outcome Measure Information:
Title
ORR
Description
overall response rate
Time Frame
Time Frame: 21days after the end of treatment
Secondary Outcome Measure Information:
Title
PFS
Description
Progression Free Survival
Time Frame
Time Frame: From date of first day of treatment until the date of first documented progression, assessed up to 24 months
Title
OS
Description
Overall Survival
Time Frame
Time Frame: From date of first day of treatment until the date of first documented date of death from any cause, assessed up to 24 months
Title
AE and SAE
Description
Adverse event and serious adverse event
Time Frame
Time Frame: From date of first day of treatment until 30 day after last treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haiyan Yang, PhD
Phone
0086-571-88122192
Email
yanghy@zjcc.org.cn
First Name & Middle Initial & Last Name & Degree
Xi Chen, MD
Phone
0086-571-88122192
Email
zjuchenxi@126.com
First Name & Middle Initial & Last Name & Degree
Xi Chen, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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ZR2 Sequential Immunochemotherapy for Newly Treated MCL

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