Clinical trial NCT03250962: SHR-1210 Alone or in Combination With Decitabine in Relapsed or Refractory Hodgkin Lymphoma
Official title: Anti-PD-1 Antibody SHR-1210 Alone or in Combination With Decitabine in Relapsed or Refractory Hodgkin Lymphoma:an Open-label Phase II Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hodgkin Lymphoma
Keywords: Relapsed/Refractory; Hodgkin Lymphoma；Decitabine; SHR-1210
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
First posted: 2017-08-16
Enrollment: 280
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: stage I: Number of Subjects with treatment-related adverse events (AEs)
timeFrame: 2 years
measure: stage I: CRR assess by investigators per the 2014 Lugano classification
timeFrame: 3 years
measure: stage II: duration of CR
timeFrame: 5 years
Secondary outcomes:
measure: stage II: duration of response
timeFrame: 5 years
measure: stage II: Progression free survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Biotherapeutic Department of Chinese PLA General Hospital
state: Beijing
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.