PD-1 Inhibitor Combined With Decitabine Followed by ASCT as Second-line Therapy for Relapsed or Refractory Classic Hodgkin's Lymphoma

Sponsor

Institute of Hematology & Blood Diseases Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05137886

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Young patients with relapsed or refractory classic Hodgkin's lymphoma will be treated with PD-1 inhibitor combined with decitabine as second-line salvage treatment for four cycles. If PR or CR was obtained after salvage treatment, patients will receive GBM conditioning regimen followed by ASCT as consolidation therapy. High-risk R/R cHL patients will be treated with PD-1 inhibitor after ASCT for 1 year. The purpose of current study is to determine the clinical efficacy and safety of PD-1 inhibitor combined with decitabine followed by ASCT as second-line treatment in patients with relapsed or refractory classic Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Lymphoma, Adult Relapse Refractory Hodgkin Lymphoma	Drug: PD-1 inhibitor	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

47 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

PD-1 Inhibitor Combined With Decitabine Followed by ASCT as Second-line Therapy for Relapsed or Refractory Classic Hodgkin's Lymphoma

Anticipated Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PD-1 inhibitor combined with decitabine followed by ASCT Patients will receive salvage treatment of PD-1 inhibitor Tislelizumab combined with decitabine for four cycles, If PR or CR was obtained after salvage treatment, patients will receive GBM (gemcitabine, bulsufan and melphalan) conditioning regimen followed by ASCT. High-risk patients will receive PD-1 inhibitor for 1 year after ASCT as maintenance therapy.	Drug: PD-1 inhibitor decitabine 10mg on d1-5, Tislelizumab 200mg on d8，21 days as one cycle. Other Names: decitabine autologous stem cell transplantation

Arm

Intervention/Treatment

Experimental: PD-1 inhibitor combined with decitabine followed by ASCT

Patients will receive salvage treatment of PD-1 inhibitor Tislelizumab combined with decitabine for four cycles, If PR or CR was obtained after salvage treatment, patients will receive GBM (gemcitabine, bulsufan and melphalan) conditioning regimen followed by ASCT. High-risk patients will receive PD-1 inhibitor for 1 year after ASCT as maintenance therapy.

Drug: PD-1 inhibitor

decitabine 10mg on d1-5, Tislelizumab 200mg on d8，21 days as one cycle.

Other Names:

decitabine

autologous stem cell transplantation

Outcome Measures

Primary Outcome Measures

Progression-free survival [2 years]
PFS

Secondary Outcome Measures

Objective response rate [2 years]
ORR
Complete response rate [2 years]
CRR
Duration of response [2 years]
DOR
Overall survival rate [2 years]
OS
Severity of the adverse events [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must have histological confirmation of relapsed or refractory classic Hodgkin lymphoma (HL).
18 to 65 years of age.
Subjects with lymphoma must have at least one measureable lesion >1 cm as defined by lymphoma response criteria.
Proper functioning of the major organs: 1) The absolute value of neutrophils (≥1×10^{9/L); 2) platelet count (≥75×10}9/L); 3) Serum creatinine <1.5 times Upper Limit Normal (ULN) ; 4) Serum total bilirubin < 1.5 times ULN; 5) Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) ≤3 times ULN; 6) Serum creatinine (Cr) ≤2 ULN, or glomerular filtration rate ≥40ml/min; 7) Thyrotropin (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) were all within the normal range (±10%).
Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
LVEF value measured by echocardiography ≥50%.
Life expectancy > 3 months.

Exclusion Criteria:

Patients with central nervous system involvement by lymphoma.
Patients with active autoimmune diseases requiring systematic treatment in the past two years (hormone replacement therapy is not considered systematic treatment, such as type I diabetes mellitus, hypothyroidism requiring only thyroxine replacement therapy, adrenocortical dysfunction or pituitary dysfunction requiring only physiological doses of glucocorticoid replacement therapy); Patients with autoimmune diseases who do not require systematic treatment within two years can be enrolled.
Known systemic vasculitides, primary or secondary immunodeficiency(such as HIV infection or severe inflammatory disease).
Pregnant or breastfeeding women.
Major surgery within 4 weeks before enrollment.
Impaired cardiac function:Ejection fraction <50% on MUGA scan. QTc interval > 450msecs on baseline ECG. Myocardial infarction within 6 months prior to starting study; other clinically significant heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension, uncontrolled arrhythmias).
Other concurrent severe and/or uncontrolled medical conditions: Patients with another primary malignant disease, except those that do not currently require treatment; acute or chronic liver, pancreatic or severe renal disease; another severe and/or life-threatening medical disease.