A Study of MIL62 Combined With Orelabrutinib for the Treatment of R/R CD20+B Cell Lymphoma
Study Details
Study Description
Brief Summary
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
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Single Arm
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Drug: Orelabrutinib
BTK inhibitor Orelabrutinib low dose or high dose; Part A:28days/cycle, Cycle1:35days; Part B:21 days/cycle, Cycle1:28days.
Drug: Recombinant humanized monoclonal antibody MIL62 injection
Recombinant humanized monoclonal antibody MIL62 injection, 800mg or1000mg each time, Part A:28days/cycle, Cycle1:35days; Part B:21 days/cycle, Cycle1:28days.
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Outcome Measures
Primary Outcome Measures
- Dose limiting toxicity (DLT)(Dose escalation phase) [At the end of Cycle 1 (each cycle is 28 days)]
Safety observation indicator
- Maximum tolerated dose (MTD) (Dose escalation phase) [At the end of Cycle 1 (each cycle is 28 days)]
Safety observation indicator
- Recommended dose for phase 2 trials of two-drug combinations (RP2D) (Dose escalation phase) [At the end of Cycle 1 (each cycle is 28 days)]
Safety observation indicator
- objective remission rate(ORR) (Dose expansion phase) [At the end of Cycle 30 (each cycle is 28 days)]
Efficacy observation indicator
Secondary Outcome Measures
- objective remission rate(ORR) [At the end of Cycle 30 (each cycle is 28 days)]
Efficacy observation indicator
- Area under the plasma concentration vs time curve(AUC) [At the end of Cycle 6 (each cycle is 28 days)]
pharmacokinetic parameter of MIL62 combined with Orelabrutinib in the treatment
- Apparent half-life for designated elimination phases (t½) [At the end of Cycle 6 (each cycle is 28 days)]
pharmacokinetic parameter of MIL62 combined with Orelabrutinib in the treatment
- The peak plasma concentration (Cmax) [At the end of Cycle 6 (each cycle is 28 days)]
pharmacokinetic parameter of MIL62 combined with Orelabrutinib in the treatment
- Duration of remission(DOR) [3 years after first treatment]
Efficacy observation indicator
- Progression-free survival(PFS) in the treatment of R/R CD20+B cell lymphoma [3 years after first treatment]
Preliminary evaluation of MIL62 combined with Orelabrutinib in the treatment of relapsed/refractory CD20+B cell lymphoma with 3-year progression-free survival
- overall survival(OS) in the treatment of R/R CD20+B cell lymphoma [3 years after first treatment]
Preliminary evaluation of MIL62 combined with Orelabrutinib in the treatment of recurrent/refractory CD20+B cell lymphoma with 3-year overall survival
- Duration of remission(DOR) in the treatment of R/R NHL [3 years after first treatment]
Preliminary evaluation of remission duration of MIL62 combined with Orelabrutinib in the treatment of Recurrent/refractory Non Hodgkin Lymphoma
- Progression-free survival(PFS) in the treatment of R/R NHL [3 years after first treatment]
Preliminary evaluation of MIL62 combined with Orelabrutinib in the treatment of Recurrent/refractory Non Hodgkin Lymphoma with 3-year progression-free survival
- overall survival(OS) in the treatment of R/R NHL [3 years after first treatment]
Preliminary evaluation of MIL62 combined with Orelabrutinib in the treatment of Recurrent/refractory Non Hodgkin Lymphoma with 3-year overall survival
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥18 years, gender not limited
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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;
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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;
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Eastern cancer collaboration group(ECOG) physical status score: 0-2
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Laboratory tests performed within 7 days prior to the first acceptance of the study drug met the protocol criteria.
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Expected survival ≥6 months
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Sign a written informed consent.
Exclusion Criteria:
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Expansion stage: DLBCL transformed from follicular lymphoma, DLBCL with follicular lymphoma, and lymphomas with primary or central nervous system involvement.
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Received any of the anti-tumor treatments(note in the protocol) before the first study drug.
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Previous use of any anticancer vaccine.
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Patients who had received hematopoietic stem cell transplantation within 3 months before the first administration
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Patients scheduled for major surgery within 28 days prior to initial administration or during the expected study period.
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Patients who Is participating in other clinical trials or first administration less than 28 days after the end of the previous clinical trial.
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Receiving prednisone treatment or other corticosteroid treatment with the same dose as prednisone ;Patients who require warfarin or an equivalent vitamin K antagonist;
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During the study period, drugs with moderate or severe inhibition or strong induction of cytochrome CYP3A4 were taken together;
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Subject has a history of any of the diseases note in the protocol;
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Patients with infections;
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Impact testing scheme compliance or other serious results explain the poor control of the merger of the disease(note in the protocol);
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Toxicity of any previous anticancer treatment has not recovered to ≤1, except for hair loss;
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A history of severe allergic reactions to humanized monoclonal antibodies or known allergies to any component of Orelabrutinib or MIL62;
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Inability to swallow research drugs, or the presence of conditions that significantly affect gastrointestinal function;
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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;
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Pregnant and lactating women; For women of childbearing age who have not undergone sterilization surgery: do not agree to use appropriate methods of contraception;
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For men not undergoing sterilization: do not agree to use the barrier method of contraception;
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Other circumstances considered inappropriate for the study by the investigator.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | The First Affiliated Hospital of Bengbu Medical College | Bengbu | Anhui | China | 100000 |
2 | Beijing Hospital | Beijing | Beijing | China | 100000 |
3 | Beijing Shijitan hospital, capital medical university | Beijing | Beijing | China | 100000 |
4 | Cancer hospital, Chinese academy of medical sciences | Beijing | Beijing | China | 100000 |
5 | Affiliated Hospital of Hebei University | Baoding | Hebei | China | 100000 |
6 | Henan Tumor Hospital | Zhengzhou | Henan | China | 100000 |
7 | Hunan Cancer Hospital | Changsha | Hunan | China | 100000 |
8 | First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China | 100000 |
9 | The First Hospital of Jilin University | Changchun | Jilin | China | 100000 |
10 | Tianjin People's Hospital | Tianjin | Tianjin | China | 100000 |
Sponsors and Collaborators
- Beijing InnoCare Pharma Tech Co., Ltd.
Investigators
- Principal Investigator: Yuankai Shi, PhD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- MIL62-CT03