SHR-1210 Alone or in Combination With Decitabine in Relapsed or Refractory Hodgkin Lymphoma

NCT ID: NCT03250962

Last Updated: 2019-04-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-11
• Study Completion Date: 2025-03-21

Brief Summary

This is a two-stage, Phase II clinical trial for patients with relapsed or refractory Hodgkin Lymphoma. The purpose of stage I is to evaluate whether treatment with the study drug decitabine in combination with SHR-1210 is safe and more effective than treatment with SHR-1210 alone; and reverse the resistance of anti-PD-1 antibody in patients with HL who had previously treated with anti-PD-1 monotherapy. If it is deemed that the combination therapy is more efficacious than SHR-1210 monotherapy (The CR rate of the combination group is at least 30% higher compared to monotherapy group with a minimal follow-up of 6 months in predicting 60 subjects naïve to anti-PD-1 antibody who are randomly assigned (2:1) to the above two groups), the stage II study will be revised to a multicohort, decitabine-plus-SHR1210 single-arm clinical trial. The primary objective of stage II study is to evaluate the long-term response duration with decitabine-plus-SHR-1210 in relapsed or refractory Hodgkin Lymphoma.

Conditions

Hodgkin Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SHR-1210-plus-Decitabine

Decitabine 10 mg/day, days 1-5; SHR-1210 200 mg, day 8, every 3 weeks.

Group Type: EXPERIMENTAL

SHR-1210

Intervention Type: DRUG

SHR-1210 is a humanized anti-PD-1 monoclonal antibody.

Decitabine

Intervention Type: DRUG

Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.

SHR-1210

SHR-1210 200 mg, day 1, every 3 weeks.

Group Type: EXPERIMENTAL

SHR-1210

Intervention Type: DRUG

SHR-1210 is a humanized anti-PD-1 monoclonal antibody.

Interventions

SHR-1210

SHR-1210 is a humanized anti-PD-1 monoclonal antibody.

Intervention Type: DRUG

Decitabine

Decitabine is an investigational (experimental) drug that works by depleting DNA methyltransferase 1 (DNMT1), which can increase tumor antigens and HLA expression, enhances antigen processing, promotes T cell infiltration, and boosts effector T cell function.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1 Subjects must have histological confirmation of relapsed or refractory Hodgkin lymphoma (HL).

2 12 to 75 years of age. 3 ECOG performance of less than 2. 4 Life expectancy of at least 3 months. 5 Subjects with lymphoma must have at least one measureable lesion >1 cm as defined by lymphoma response criteria.

6 Subjects must have received at least four prior chemotherapy regimen, and must be off therapy for at least 4 weeks prior to Day 1. Subjects with autologous hematopoietic stem-cell transplantation are eligible which must be more than 3 months.Subjects with Anti-PD-1 antibody are eligible which must be resistance.

7 Subjects must have adequate marrow, live, renal and heart functions.

Exclusion Criteria

• 1 Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.

2 Serious uncontrolled medical disorders or active infections, pulmonary infection especially.

3 Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month .

4 Prior organ allograft. 5 Women who are pregnant or breastfeeding. 6 Women with a positive pregnancy test on enrollment or prior to investigational product administration.

7 Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese PLA General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Han weidong

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Facility Contacts

Weidong Han, M.D

Role: primary

hanwdrsw@sina.com

+86-10-66937463

Qingming Yang, M.D

Role: backup

yangqm@medmail.com.cn

+86-10-55499341

References

Nie J, Wang C, Liu Y, Yang Q, Mei Q, Dong L, Li X, Liu J, Ku W, Zhang Y, Chen M, An X, Shi L, Brock MV, Bai J, Han W. Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed/Refractory Classical Hodgkin Lymphoma. J Clin Oncol. 2019 Jun 10;37(17):1479-1489. doi: 10.1200/JCO.18.02151. Epub 2019 Apr 30.

Reference Type: DERIVED

PMID: 31039052 (View on PubMed)

Liu Y, Wang C, Li X, Dong L, Yang Q, Chen M, Shi F, Brock M, Liu M, Mei Q, Liu J, Nie J, Han W. Improved clinical outcome in a randomized phase II study of anti-PD-1 camrelizumab plus decitabine in relapsed/refractory Hodgkin lymphoma. J Immunother Cancer. 2021 Apr;9(4):e002347. doi: 10.1136/jitc-2021-002347.

Reference Type: DERIVED

PMID: 33820822 (View on PubMed)

Wang C, Liu Y, Dong L, Li X, Yang Q, Brock MV, Mei Q, Liu J, Chen M, Shi F, Liu M, Nie J, Han W. Efficacy of Decitabine plus Anti-PD-1 Camrelizumab in Patients with Hodgkin Lymphoma Who Progressed or Relapsed after PD-1 Blockade Monotherapy. Clin Cancer Res. 2021 May 15;27(10):2782-2791. doi: 10.1158/1078-0432.CCR-21-0133. Epub 2021 Mar 5.

Reference Type: DERIVED

PMID: 33674274 (View on PubMed)

Other Identifiers

CHN-PLAGH-BT-023

Identifier Type: -

Identifier Source: org_study_id