Clinical trial NCT04425824: Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma
Official title: Toripalimab Combine With Rituximab for Treatment of Relapsed Refractory CD20 Positive Diffuse Large B-cell Lymphoma: An Exploratory Small Sample, Phase II, Single-center Clinical Trail
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Rituximab
Toripalimab
Keywords: DLBCL
CD20
Toripalimab
Rituximab
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2020-06-11
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Exploring the efficacy and safety of Toripalimab with Rituximab for treatment of relapsed refractory CD20 positive diffuse large B-cell lymphoma.

Detailed description: Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2). Rituximab is an antibody to CD20 molecules. One of the mechanisms of killing tumor cells is through antibody-dependent cell-mediated cytotoxicity (ADCC). These two drugs may have a synergistic effect on anti-tumor. The purpose of this study is to determine whether Toripalimab with Rituximab is effective and safe for treatment of relapsed refractory CD20 positive diffuse large B-cell lymphoma. This is an exploratory small sample, phase II, single-center clinical trial, which is going to enroll 20 participants.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years old;
2. According to the WHO 2016 classification criteria, the CD20 positive diffuse large B-cell lymphoma (DLBCL) diagnosed by pathology should include the indicators of immunohistochemistry: CD10, BCL-2, MUM-1, BCL-6 and C-MYC;
3. Relapsed or refractory DLBCL.Patients younger than 65 years should relapse or progress after receiving at least second-line treatment, and patients 65 years of age and older could be intolerant to second-line treatment, and they who relapse or progress after receiving first-line treatment;
4. There is at least one measurable lesion, defined as measurable dual-diameter, intra-lymph node lesion, short diameter\> 1.5cm, extra-lymph node lesion short diameter\> 1.0cm;
5. Recurrence confirmed by pathological biopsy and CD20 positive;
6. ECOG score 0-2 points;
7. No autoimmune diseases;
8. Blood routine examination meets the following criteria:

   1. Neutrophil count ≥ 1.5 x 109 / L,;
   2. Platelet ≥ 75 x 109 / L,;
   3. Hemoglobin ≥ 10.0 g / dL;
9. The main organ function meets the following criteria:

   1. Aspartate aminotransferase and alanine aminotransferase ≤ 2.0 times the upper limit of normal value;
   2. Bilirubin ≤ 2.0 mg / dL;
   3. Creatinine clearance rate ≥ 60 mL / min;
10. Patients must agree to take effective contraceptive measures during the study according to the investigator's request;
11. Understand and voluntarily sign written informed consent.

Exclusion Criteria:

1. Diagnosed as transformed diffuse large B-cell lymphoma;
2. Diagnosed as double-hit diffuse large B-cell lymphoma (DHL);
3. Diagnosed as primary or secondary central nervous system lymphoma;
4. HBV DNA positive or HCV RNA positive patients;
5. Left ventricular ejection fraction \<50%;
6. Patients with history of autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, ankylosing spondylitis
7. Patients are using or have been used immunosuppressive drugs
8. Patients with ≥2 grade peripheral neuropathy

Primary outcomes:
measure: Objective Response Rate(ORR)
timeFrame: up to 24 months
measure: Progression Free Survival(PFS)
timeFrame: up to 24 months
Secondary outcomes:
measure: To assessment of the safety events
timeFrame: up to 24 months
measure: Assessment of the correlation between tumor cell PD-L1 expression intensity and efficacy
timeFrame: up to 24 months
Other outcomes:
measure: Analysis of the correlation between the ammount of T cells and NK cells around tumor cells
timeFrame: up to 24 months
measure: Change in immune microenviroment at the time of initial diagnosis and relapse
timeFrame: up to 24 months
Locations:
city: Beijing
country: China
facility: Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Study officials:
References: