A Study of MIL62 Combined With Orelabrutinib for the Treatment of R/R CD20+B Cell Lymphoma

Study Overview
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Brief Summary
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Dose escalation and expansion phase I/IIa clinical study of recombinant humanized type II CD20 monoclonal antibody MIL62 injection combined with a novel selective Bruton Tyrosine Kinase(BTK) inhibitor Orelabrutinib in the treatment of recurrent/refractory CD20+B cell lymphoma

Official Title
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A Phase I/IIa Study on Dose-escalation and Extension of Recombinant Humanized Type II CD20 Monoclonal Antibody MIL62 Injection Combined With BTK Inhibitor Orelabrutinib in the Treatment of Recurrent/Refractory CD20+B-cell Lymphoma

Conditions
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B-cell Lymphoma Recurrent, B-cell Lymphoma Refractory

Intervention / Treatment
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* Drug: Orelabrutinib
* Drug: Recombinant humanized monoclonal antibody MIL62 injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years, gender not limited Dose escalation phase: Histologically confirmed CD20 positive B-cell non-Hodgkin's lymphoma; Expansion stage: R/R NHL Or histologically diagnosed CD20 positive chronic lymphocytic leukemia/small lymphocytic lymphoma; Dose escalation phase ：Patients who have received at least one treatment regimen Expansion stage：Patients who have received at least one to four treatment regimens with at least one regimen containing rituximab; Eastern cancer collaboration group(ECOG) physical status score: 0-2 Laboratory tests performed within 7 days prior to the first acceptance of the study drug met the protocol criteria. Expected survival ≥6 months Sign a written informed consent. Exclusion Criteria: Expansion stage: DLBCL transformed from follicular lymphoma, DLBCL with follicular lymphoma, and lymphomas with primary or central nervous system involvement. Received any of the anti-tumor treatments(note in the protocol) before the first study drug. Previous use of any anticancer vaccine. Patients who had received hematopoietic stem cell transplantation within 3 months before the first administration Patients scheduled for major surgery within 28 days prior to initial administration or during the expected study period. Patients who Is participating in other clinical trials or first administration less than 28 days after the end of the previous clinical trial. Receiving prednisone treatment or other corticosteroid treatment with the same dose as prednisone ;Patients who require warfarin or an equivalent vitamin K antagonist; During the study period, drugs with moderate or severe inhibition or strong induction of cytochrome CYP3A4 were taken together; Subject has a history of any of the diseases note in the protocol; Patients with infections; Impact testing scheme compliance or other serious results explain the poor control of the merger of the disease(note in the protocol); Toxicity of any previous anticancer treatment has not recovered to ≤1, except for hair loss; A history of severe allergic reactions to humanized monoclonal antibodies or known allergies to any component of Orelabrutinib or MIL62; Inability to swallow research drugs, or the presence of conditions that significantly affect gastrointestinal function; Hepatitis b surface antigen (HBsAg) and/or hepatitis b core antibody (HBcAb) are positive ; Hepatitis c virus (HCV) antibody positive and HCV RNA positive patients; Human immunodeficiency virus (HIV) serum response was positive; Pregnant and lactating women; For women of childbearing age who have not undergone sterilization surgery: do not agree to use appropriate methods of contraception; For men not undergoing sterilization: do not agree to use the barrier method of contraception; Other circumstances considered inappropriate for the study by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br> | Drug: Orelabrutinib<br>* BTK inhibitor Orelabrutinib low dose or high dose; Part A:28days/cycle, Cycle1:35days; Part B:21 days/cycle, Cycle1:28days.<br>Drug: Recombinant humanized monoclonal antibody MIL62 injection<br>* Recombinant humanized monoclonal antibody MIL62 injection, 800mg or1000mg each time, Part A:28days/cycle, Cycle1:35days; Part B:21 days/cycle, Cycle1:28days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT)(Dose escalation phase) | Safety observation indicator | At the end of Cycle 1 (each cycle is 28 days) | 
| Maximum tolerated dose (MTD) (Dose escalation phase) | Safety observation indicator | At the end of Cycle 1 (each cycle is 28 days) | 
| Recommended dose for phase 2 trials of two-drug combinations (RP2D) (Dose escalation phase) | Safety observation indicator | At the end of Cycle 1 (each cycle is 28 days) | 
| objective remission rate(ORR) (Dose expansion phase) | Efficacy observation indicator | At the end of Cycle 30 (each cycle is 28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective remission rate(ORR) | Efficacy observation indicator | At the end of Cycle 30 (each cycle is 28 days) | 
| Area under the plasma concentration vs time curve(AUC) | pharmacokinetic parameter of MIL62 combined with Orelabrutinib in the treatment | At the end of Cycle 6 (each cycle is 28 days) | 
| Apparent half-life for designated elimination phases (t½) | pharmacokinetic parameter of MIL62 combined with Orelabrutinib in the treatment | At the end of Cycle 6 (each cycle is 28 days) | 
| The peak plasma concentration (Cmax) | pharmacokinetic parameter of MIL62 combined with Orelabrutinib in the treatment | At the end of Cycle 6 (each cycle is 28 days) | 
| Duration of remission(DOR) | Efficacy observation indicator | 3 years after first treatment | 
| Progression-free survival(PFS) in the treatment of R/R CD20+B cell lymphoma | Preliminary evaluation of MIL62 combined with Orelabrutinib in the treatment of relapsed/refractory CD20+B cell lymphoma with 3-year progression-free survival | 3 years after first treatment | 
| overall survival(OS) in the treatment of R/R CD20+B cell lymphoma | Preliminary evaluation of MIL62 combined with Orelabrutinib in the treatment of recurrent/refractory CD20+B cell lymphoma with 3-year overall survival | 3 years after first treatment | 
| Duration of remission(DOR) in the treatment of R/R NHL | Preliminary evaluation of remission duration of MIL62 combined with Orelabrutinib in the treatment of Recurrent/refractory Non Hodgkin Lymphoma | 3 years after first treatment | 
| Progression-free survival(PFS) in the treatment of R/R NHL | Preliminary evaluation of MIL62 combined with Orelabrutinib in the treatment of Recurrent/refractory Non Hodgkin Lymphoma with 3-year progression-free survival | 3 years after first treatment | 
| overall survival(OS) in the treatment of R/R NHL | Preliminary evaluation of MIL62 combined with Orelabrutinib in the treatment of Recurrent/refractory Non Hodgkin Lymphoma with 3-year overall survival | 3 years after first treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD20+