NCT03250962

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
280

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Sep 2017

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 10, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

August 16, 2017

Completed
26 days until next milestone

Study Start

First participant enrolled

September 11, 2017

Completed
4.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 21, 2022

Completed
2.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 21, 2025

Completed
Last Updated

April 1, 2019

Status Verified

March 1, 2019

Enrollment Period

4.9 years

First QC Date

August 10, 2017

Last Update Submit

March 28, 2019

Conditions

Hodgkin Lymphoma

Keywords

Relapsed/Refractory; Hodgkin Lymphoma；Decitabine; SHR-1210

Outcome Measures

Primary Outcomes (3)

  • stage I: Number of Subjects with treatment-related adverse events (AEs)

    Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.03.

    2 years

  • stage I: CRR assess by investigators per the 2014 Lugano classification

    rate of subjects achieved complete response in all evaluable subjects

    3 years

  • stage II: duration of CR

    Time measured from the day of first documented CR to the date of first documented progression, or death from any cause.

    5 years

Secondary Outcomes (2)

  • stage II: duration of response

    5 years

  • stage II: Progression free survival

    5 years

Study Arms (2)

SHR-1210-plus-Decitabine

EXPERIMENTAL

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

Drug: SHR-1210Drug: Decitabine

SHR-1210

EXPERIMENTAL

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

Drug: SHR-1210

Interventions

SHR-1210DRUG

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

SHR-1210SHR-1210-plus-Decitabine
DecitabineDRUG

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-plus-Decitabine

Eligibility Criteria

Age12 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Subjects must have histological confirmation of relapsed or refractory Hodgkin lymphoma (HL).
  • 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.
  • 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.
  • Subjects must have adequate marrow, live, renal and heart functions.

You may not qualify if:

  • Subjects with any autoimmune disease or history of syndrome that requires corticosteroids or immunosuppressive medications.
  • Serious uncontrolled medical disorders or active infections, pulmonary infection especially.
  • Active alimentary tract hemorrhage or history of alimentary tract hemorrhage in 1 month .
  • 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.
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

Related Publications (3)

  • 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.

    PMID: 33820822DERIVED

  • 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.

    PMID: 33674274DERIVED

  • 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.

    PMID: 31039052DERIVED

MeSH Terms

Conditions

Hodgkin DiseaseRecurrence

Interventions

camrelizumabDecitabine

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AzacitidineAza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

August 10, 2017

First Posted

August 16, 2017

Study Start

September 11, 2017

Primary Completion

July 21, 2022

Study Completion

March 21, 2025

Last Updated

April 1, 2019

Record last verified: 2019-03

Data Sharing

IPD Sharing
Will not share

Study Protocol

Locations

CN(1)