Clinical Trials /

A Study of MIL62 Combined With ICP-022 for the Treatment of R/R CD20+B Cell Lymphoma

NCT04304040

Description:

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 ICP-022 in the treatment of recurrent/refractory CD20+B cell lymphoma

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of MIL62 Combined With ICP-022 for the Treatment of R/R CD20+B Cell Lymphoma
  • Official Title: A Phase I/IIa Study on Dose-escalation and Extension of Recombinant Humanized Type II CD20 Monoclonal Antibody MIL62 Injection Combined With BTK Inhibitor ICP-022 in the Treatment of Recurrent/Refractory CD20+B-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: MIL62-CT03
  • NCT ID: NCT04304040

Conditions

  • B-cell Lymphoma Recurrent
  • B-cell Lymphoma Refractory

Interventions

DrugSynonymsArms
ICP-022Single Arm
Recombinant humanized monoclonal antibody MIL62 injectionSingle Arm

Purpose

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 ICP-022 in the treatment of recurrent/refractory CD20+B cell lymphoma

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimental
  • ICP-022
  • Recombinant humanized monoclonal antibody MIL62 injection

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥18 years, gender not limited

          2. Dose escalation phase: histologically confirmed CD20 positive B cell non-Hodgkin's
             lymphoma (except for chronic lymphocytic leukemia/small lymphocytic lymphoma);
             Expansion stage: R/R Follicular Lymphoma(FL): histologically confirmed CD20 positive
             grade 1-3a follicular lymphoma with no tissue transformation. In case of suspected
             clinical transformation, biopsy of the suspected site is required to confirm no
             transformation

          3. Patients who have received at least one treatment regimen (with or without rituximab)
             without remission or progression after remission, or who are not tolerant to previous
             treatment

          4. Except for the splenic marginal region lymphoma, there was at least one
             two-dimensional measurable lesion (CT scan or MRI), namely, the longest diameter of
             the lymph node lesion was >1.5cm, the shortest diameter was >1cm, and the longest
             diameter of the extra-junction lesion was >1cm.

          5. Eastern cancer collaboration group(ECOG) physical status score: 0-2

          6. Laboratory tests performed within 7 days prior to the first acceptance of the study
             drug met the following criteria: 1) platelet count ≥75 x 109/L, neutrophils ≥1.5 x
             109/L, hemoglobin ≥9g/dL, if accompanied by bone marrow invasion, platelet ≥50×109/L,
             neutrophils absolute value ≥1.0×109/L;2) glutamic oxalacetic transaminase (AST) or
             glutamic-pyruvic transaminase (ALT) ≤ 2.5 x ULN;3) total bilirubin ≤ 1.5x Upper Limit
             of Normal(ULN); Renal creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault
             formula);4) prothrombin time (PT)/international normalized ratio(INR) ≤1.5 x ULN.

          7. Expected survival ≥6 months

          8. Sign a written informed consent.

        Exclusion Criteria:

          1. Received any of the following anti-tumor treatments before the first study drug: (1)
             received any monoclonal antibody within 3 months;(2) received chemotherapy within 28
             days;(3) received anti-tumor Chinese (herbal) drug treatment within 28 days (2 doses
             or more);(4) received radiotherapy within 42 days;(5) received other anti-tumor
             treatment within 28 days, such as BTK kinase inhibitor, Phosphatidylinositol -3-
             hydroxykinase(PI3K) inhibitor treatment;6. Received obinutuzumab (Gazyva, GA101)
             treatment within 12 months;

          2. Previous use of any anticancer vaccine

          3. Patients who had received hematopoietic stem cell transplantation within 3 months
             before the first administration or who planned to receive hematopoietic stem cell
             transplantation within 3 months

          4. Patients scheduled for major surgery within 28 days prior to initial administration or
             during the expected study period, except for diagnostic surgery

          5. Participated in other clinical trials within 28 days prior to first receiving the drug
             under study, or plan to participate in other clinical trials at the same time as this
             study

          6. Receiving prednisone treatment ≥20mg/ day or other corticosteroid treatment with the
             same dose as prednisone (if the dose can be kept stable below the dose level within 7
             days before the baseline CT examination (<20mg/ day can be included);Patients who
             require warfarin or an equivalent vitamin K antagonist;

          7. During the study period, drugs with moderate or severe inhibition or strong induction
             of cytochrome CYP3A4 were taken together

          8. Subject has a history of any of the following diseases: central nervous system
             lymphoma or leukemia; Had other malignant tumors in the past 3 years, except basal or
             squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the
             cervix or breast that had received radical treatment;(3) progressive multifocal
             leukoencephalopathy (PML);(4) a history of stroke or intracranial hemorrhage within 6
             months prior to receiving the study drug for the first time; Serious hemorrhagic
             diseases such as hemophilia A, hemophilia B, von Willebrand disease or spontaneous
             bleeding requiring blood transfusion or other medical intervention;

          9. Patients with active bacteria, viruses, fungi, mycobacteria, parasites or other
             infections (excluding nail bed fungal infections) and requiring intravenous antibiotic
             treatment before enrollment

         10. Impact testing scheme compliance or other serious results explain the poor control of
             the merger of the disease, including the clinical significance of cardiovascular
             disease (such as New York heart association class III or IV heart disease, myocardial
             within the past 6 months, obstruction or unstable type of arrhythmia, or unstable
             angina) or lung disease (including obstructive pulmonary disease (COPD) and history of
             bronchospasm);

         11. Toxicity of any previous anticancer treatment has not recovered to ≤1, except for hair
             loss

         12. A history of severe allergic reactions to humanized monoclonal antibodies or known
             allergies to any component of icp-022 or MIL62

         13. Inability to swallow research drugs, or the presence of conditions that significantly
             affect gastrointestinal function, such as malabsorption syndrome, gastric or small
             bowel resection, symptomatic inflammatory bowel disease, or partial or complete
             intestinal obstruction

         14. Hepatitis b surface antigen (HBsAg) and/or hepatitis b core antibody (HBcAb) are
             positive and Hepatitis B Virus(HBV) DNA exceeds the normal range; Hepatitis b surface
             antigen (HBsAg) and/or hepatitis b core antibody (HBcAb) positive do not agree to
             regular DNA testing, or do not receive antiviral preventive treatment; Hepatitis c
             virus (HCV) antibody positive and HCV RNA positive patients; Human immunodeficiency
             virus (HIV) serum response was positive;

         15. Pregnant and lactating women; For women of childbearing age who have not undergone
             sterilization surgery: do not agree to use appropriate methods of contraception, such
             as oral contraceptives, intrauterine devices, barrier contraception or spermicide,
             during treatment and for at least 12 months after the last administration of the drug
             under study;

         16. For men not undergoing sterilization: do not agree to use the barrier method of
             contraception during the study period and for at least 12 months after the last
             administration of the study drug, and do not agree to request their spouse to use
             other methods of contraception, such as oral contraceptives, intrauterine devices,
             barrier methods of contraception or spermicide;

         17. Other circumstances considered inappropriate for the study by the investigator.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose limiting toxicity (DLT)(Dose escalation phase)
Time Frame:At the end of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Safety observation indicator

Secondary Outcome Measures

Measure:objective remission rate(ORR)
Time Frame:At the end of Cycle 30 (each cycle is 28 days)
Safety Issue:
Description:Efficacy observation indicator
Measure:Area under the plasma concentration vs time curve(AUC)
Time Frame:At the end of Cycle 6 (each cycle is 28 days)
Safety Issue:
Description:pharmacokinetic parameter of MIL62 combined with ICP-022 in the treatment
Measure:Apparent half-life for designated elimination phases (t½)
Time Frame:At the end of Cycle 6 (each cycle is 28 days)
Safety Issue:
Description:pharmacokinetic parameter of MIL62 combined with ICP-022 in the treatment
Measure:The peak plasma concentration (Cmax)
Time Frame:At the end of Cycle 6 (each cycle is 28 days)
Safety Issue:
Description:pharmacokinetic parameter of MIL62 combined with ICP-022 in the treatment
Measure:Duration of remission(DOR)
Time Frame:3 years after first treatment
Safety Issue:
Description:Efficacy observation indicator
Measure:Progression-free survival(PFS) in the treatment of R/R CD20+B cell lymphoma
Time Frame:3 years after first treatment
Safety Issue:
Description:Preliminary evaluation of MIL62 combined with ICP-022 in the treatment of relapsed/refractory CD20+B cell lymphoma with 3-year progression-free survival
Measure:overall survival(OS) in the treatment of R/R CD20+B cell lymphoma
Time Frame:3 years after first treatment
Safety Issue:
Description:Preliminary evaluation of MIL62 combined with ICP-022 in the treatment of recurrent/refractory CD20+B cell lymphoma with 3-year overall survival
Measure:Duration of remission(DOR) in the treatment of R/R FL
Time Frame:3 years after first treatment
Safety Issue:
Description:Preliminary evaluation of remission duration of MIL62 combined with ICP-022 in the treatment of Recurrent/refractory follicular lymphoma
Measure:Progression-free survival(PFS) in the treatment of R/R FL
Time Frame:3 years after first treatment
Safety Issue:
Description:Preliminary evaluation of MIL62 combined with ICP-022 in the treatment of Recurrent/refractory follicular lymphoma with 3-year progression-free survival
Measure:overall survival(OS) in the treatment of R/R FL
Time Frame:3 years after first treatment
Safety Issue:
Description:Preliminary evaluation of MIL62 combined with ICP-022 in the treatment of Recurrent/refractory follicular lymphoma with 3-year overall survival

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Beijing InnoCare Pharma Tech Co., Ltd.

Trial Keywords

  • CD20+

Last Updated

March 9, 2020