Clinical trial NCT04304040: A Study of MIL62 Combined With Orelabrutinib 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 Orelabrutinib in the Treatment of Recurrent/Refractory CD20+B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: B-cell Lymphoma Recurrent
B-cell Lymphoma Refractory
Keywords: CD20+
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-03-11
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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; Expansion stage: R/R NHL Or histologically diagnosed CD20 positive chronic lymphocytic leukemia/small lymphocytic lymphoma;
3. 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;
4. Eastern cancer collaboration group(ECOG) physical status score: 0-2
5. Laboratory tests performed within 7 days prior to the first acceptance of the study drug met the protocol criteria.
6. Expected survival ≥6 months
7. Sign a written informed consent.

Exclusion Criteria:

1. Expansion stage: DLBCL transformed from follicular lymphoma, DLBCL with follicular lymphoma, and lymphomas with primary or central nervous system involvement.
2. Received any of the anti-tumor treatments(note in the protocol) before the first study drug.
3. Previous use of any anticancer vaccine.
4. Patients who had received hematopoietic stem cell transplantation within 3 months before the first administration
5. Patients scheduled for major surgery within 28 days prior to initial administration or during the expected study period.
6. Patients who Is participating in other clinical trials or first administration less than 28 days after the end of the previous clinical trial.
7. Receiving prednisone treatment or other corticosteroid treatment with the same dose as prednisone ;Patients who require warfarin or an equivalent vitamin K antagonist;
8. During the study period, drugs with moderate or severe inhibition or strong induction of cytochrome CYP3A4 were taken together;
9. Subject has a history of any of the diseases note in the protocol;
10. Patients with infections;
11. Impact testing scheme compliance or other serious results explain the poor control of the merger of the disease(note in the protocol);
12. Toxicity of any previous anticancer treatment has not recovered to ≤1, except for hair loss;
13. A history of severe allergic reactions to humanized monoclonal antibodies or known allergies to any component of Orelabrutinib or MIL62;
14. Inability to swallow research drugs, or the presence of conditions that significantly affect gastrointestinal function;
15. 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;
16. Pregnant and lactating women; For women of childbearing age who have not undergone sterilization surgery: do not agree to use appropriate methods of contraception;
17. For men not undergoing sterilization: do not agree to use the barrier method of contraception;
18. Other circumstances considered inappropriate for the study by the investigator.

Primary outcomes:
measure: Dose limiting toxicity (DLT)(Dose escalation phase)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Maximum tolerated dose (MTD) (Dose escalation phase)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Recommended dose for phase 2 trials of two-drug combinations (RP2D) (Dose escalation phase)
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: objective remission rate(ORR) (Dose expansion phase)
timeFrame: At the end of Cycle 30 (each cycle is 28 days)
Secondary outcomes:
measure: objective remission rate(ORR)
timeFrame: At the end of Cycle 30 (each cycle is 28 days)
measure: Area under the plasma concentration vs time curve(AUC)
timeFrame: At the end of Cycle 6 (each cycle is 28 days)
measure: Apparent half-life for designated elimination phases (t½)
timeFrame: At the end of Cycle 6 (each cycle is 28 days)
measure: The peak plasma concentration (Cmax)
timeFrame: At the end of Cycle 6 (each cycle is 28 days)
measure: Duration of remission(DOR)
timeFrame: 3 years after first treatment
measure: Progression-free survival(PFS) in the treatment of R/R CD20+B cell lymphoma
timeFrame: 3 years after first treatment
measure: overall survival(OS) in the treatment of R/R CD20+B cell lymphoma
timeFrame: 3 years after first treatment
measure: Duration of remission(DOR) in the treatment of R/R NHL
timeFrame: 3 years after first treatment
measure: Progression-free survival(PFS) in the treatment of R/R NHL
timeFrame: 3 years after first treatment
measure: overall survival(OS) in the treatment of R/R NHL
timeFrame: 3 years after first treatment
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Shijitan hospital, capital medical university
state: Beijing
city: Beijing
country: China
facility: Cancer hospital, Chinese academy of medical sciences
state: Beijing
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Suzhou
country: China
facility: First Affiliated Hospital of Soochow University
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Tianjin
country: China
facility: Tianjin People's Hospital
state: Tianjin
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi, PhD
role: PRINCIPAL_INVESTIGATOR
References: