Hodgkin Lymphoma, Adult
Conditions
Brief summary
This is an open-label, multicenter, non-randomized, phase 2 trial to evaluate efficacy and safety of SHR-1210 in patients with relapsed or refractory classic Hodgkin's lymphoma. The primary objective is to assess ORR of SHR-1210 in patients with relapsed or refractory classic Hodgkin's lymphoma.
Detailed description
The primary objective of this phase 2 study is to assess objective response rate of SHR-1210 in patients with relapsed or refractory classic Hodgkin's lymphoma. The secondary objective is to observe the duration of response, progression free survival, time to response, overall survival and safety of SHR-1210 in relapsed or refractory classic Hodgkin's lymphoma. Pharmacokinetic index is also investigated in 12 patients.
Interventions
DRUGSHR-1210
A humanized monoclonal immunoglobulin
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed classic Hodgkin's lymphoma; 2. Relapsed or refractory cHL and meet any of the following criterions: a) did not achieve remission or progression after autologous hematopoietic stem cell transplantation. b) at least 2 lines of systemic chemotherapy and are not suitable for autologous stem cell transplantation; 3. Subjects enrolled have measurable lesion (s) according to Lugano 2014 criteria; 4. ECOG performance status of 0 or 1; 5. Life expectancy ≥ 12 weeks; 6. Adequate laboratory parameters during the screening period as evidenced by the following: 1. Absolute neutrophil count ≥ 1.0 × 109/L; 2. Platelets ≥ 75 × 109/L; 3. Hemoglobin ≥ 8.0 g/dL; 4. Total bilirubin (TBIL) \< 1.5 × upper limit of normal (ULN), ALT and AST ≤ 2.5×ULN; 5. Serum Creatinine ≤1.25×ULN or Creatinine clearance≥45 mL/min; 6. Coagulation function index: INR ≤1.5×ULN，APTT≤1.5×ULN; 7. Women of childbearing potential (WOCBP) must be willing and able to employ a highly effective method of birth control/contraception to prevent pregnancy while on treatment and for at least 60 days after receiving the last dose of study treatment. Women of childbearing potential with pregnancy test negative within 7 days before entering the group; male subjects with WOCBP partner should receive Surgical sterilization or consent to employ a highly effective method of birth control/contraception to prevent pregnancy while on treatment and for at least 120 days after receiving the last dose of study treatment; 8. Able to understand and sign an informed consent form (ICF).
Exclusion criteria
1. Known nodular lymphoma predominant Hodgkin lymphoma or Grey zone lymphoma. 2. Known central nervous system lymphoma. 3. History and complication: (1) Active, known or suspected autoimmune disease. Subjects who were in a stable state without systemic immunosuppressive therapy were admitted; (2) Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic corticosteroids \> 10mg; doses \> 10 mg/day topical prednisone or equivalent are prohibited within 2 weeks before entering the group; (3) Received anti-tumor vaccines or other anti-tumor therapy with immune stimulation within 3 months before the first dose SHR-1210; (4) Prior exposure to any PD-1/PD-L1/PD -L 2 or CTLA -4 antibody; (5) Participating in other clinical studies or less than 4 weeks before the end of a clinical trial; (6) Known and highly Suspicion of interstitial pneumonia; (7) Other active malignancies that required treating. (subjects with skin basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma or cervical carcinoma who had no disease recurrence within 5 years after the start of treatment were excluded); (8) Received chemotherapy, radiotherapy, immunotherapy, including topical therapy within 4 weeks. Previous anti-tumor therapy related adverse reactions (except hair loss) did not recover to CTCAE ≤1; (9) Prior allo-HSCT; (10) ASCT within 90 days; (11) Impact of major surgery or severe trauma had been eliminated for less than 14 days; (12) Active pulmonary tuberculosis; (13) Severe acute or chronic infection requiring systemic therapy; (14) Suffering from heart failure (New York Heart Association standard III and given appropriate medical treatment. Uncontrolled coronary artery disease and arrhythmia. History of myocardial infarction within 6 months; (15) Inoculated with live vaccine within 4 weeks before receiving the investigational drug. Injections of inactivated influenza vaccine for seasonal influenza are permitted, but not live attenuated influenza vaccines for intranasal use. 4\. laboratory test: (1) known HIV positive or known AIDS; (2) Untreated active hepatitis; co-infection with hepatitis B and hepatitis C. 5\. Other factors that may lead to the study termination, such as severe disease or abnormal laboratory tests or family or social factors affecting subjects safety or test data and sample collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR Assess by IRC | CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25. ORR of 36 weeks based on CT and PET were reported. | rate of subjects achieved complete response plus partial response in all evaluable subjects (Response was assessed with CT and PET using 2014 Lugano Criteria for Malignant Lymphomas, CR is disappearance of all tumor lesions, PR is over 50% decrease of the sum of the product of the perpendicular diameters from baseline ;overall response:PR+CR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DoR Assess by IRC | CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25. DoR of 36 weeks based on CT and PET were reported. | Duration of Response (Response was assessed with CT and PET using 2014 Lugano Criteria for Malignant Lymphomas, disease progression is over 50% increase of an product of perpendicular diameters of any target lesion from nadir with any diameter increased over 0.5cm for lesions \<=2cm or increased by 1cm for lesions \>2cm，or appearance of new lesions, or progression of non-target lesion ) |
| PFS Assess by IRC | Up to 3 years | Progression-free Survival (Response was assessed with CT and PET using 2014 Lugano Criteria for Malignant Lymphomas, disease progression is over 50% increase of an product of perpendicular diameters of any target lesion from nadir with any diameter increased over 0.5cm for lesions \<=2cm or increased by 1cm for lesions \>2cm，or appearance of new lesions, or progression of non-target lesion ) |
| TTR Assess by IRC | CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25. | Time to response (Response was assessed with CT and PET using 2014 Lugano Criteria for Malignant Lymphomas, CR is disappearance of all tumor lesions, PR is over 50% decrease of the sum of the product of the perpendicular diameters from baseline ;overall response:PR+CR) |
| OS | Up to 3 years | Overall Survival |
| Incidence and Severity of Adverse Events (AE) | Up to 3 years | — |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Injection SHR-1210 SHR-1210 injection, 200 mg/dose, intravenous infusion. | 75 |
| Total | 75 |
Baseline characteristics
| Characteristic | Injection SHR-1210 |
|---|---|
| Age, Continuous | 34 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 75 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 75 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 75 |
| other Total, other adverse events | 74 / 75 |
| serious Total, serious adverse events | 12 / 75 |
Outcome results
Primary
ORR Assess by IRC
rate of subjects achieved complete response plus partial response in all evaluable subjects (Response was assessed with CT and PET using 2014 Lugano Criteria for Malignant Lymphomas, CR is disappearance of all tumor lesions, PR is over 50% decrease of the sum of the product of the perpendicular diameters from baseline ;overall response:PR+CR)
Time frame: CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25. ORR of 36 weeks based on CT and PET were reported.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Injection SHR-1210 | ORR Assess by IRC | 76.0 percentage |
Secondary
DoR Assess by IRC
Duration of Response (Response was assessed with CT and PET using 2014 Lugano Criteria for Malignant Lymphomas, disease progression is over 50% increase of an product of perpendicular diameters of any target lesion from nadir with any diameter increased over 0.5cm for lesions \<=2cm or increased by 1cm for lesions \>2cm，or appearance of new lesions, or progression of non-target lesion )
Time frame: CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25. DoR of 36 weeks based on CT and PET were reported.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Injection SHR-1210 | DoR Assess by IRC | 31.7 months |
Secondary
Incidence and Severity of Adverse Events (AE)
Time frame: Up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Injection SHR-1210 | Incidence and Severity of Adverse Events (AE) | 75 participants |
Secondary
OS
Overall Survival
Time frame: Up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Injection SHR-1210 | OS | NA months |
Secondary
PFS Assess by IRC
Progression-free Survival (Response was assessed with CT and PET using 2014 Lugano Criteria for Malignant Lymphomas, disease progression is over 50% increase of an product of perpendicular diameters of any target lesion from nadir with any diameter increased over 0.5cm for lesions \<=2cm or increased by 1cm for lesions \>2cm，or appearance of new lesions, or progression of non-target lesion )
Time frame: Up to 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Injection SHR-1210 | PFS Assess by IRC | 22.5 months |
Secondary
TTR Assess by IRC
Time to response (Response was assessed with CT and PET using 2014 Lugano Criteria for Malignant Lymphomas, CR is disappearance of all tumor lesions, PR is over 50% decrease of the sum of the product of the perpendicular diameters from baseline ;overall response:PR+CR)
Time frame: CT was conducted at baseline, at weeks 9, 17, 25, 37, 49, 65, 81, and 97, and then every 26 weeks; PET was conducted at baseline, weeks 17 and 25.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Injection SHR-1210 | TTR Assess by IRC | 2.0 months |