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

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.

Study Overview

• Status: Recruiting
• Conditions: Refractory Hodgkin Lymphoma; Relapse; Hodgkin Lymphoma, Adult
• Intervention / Treatment: Drug: PD-1 inhibitor

• Study Type: Interventional
• Enrollment (Anticipated): 47
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Dehui Zou, Dr.; Phone Number: 86-022-23909282; Email: zoudehui@ihcams.ac.cn
• Study Contact Backup: Name: Huimin Liu, Dr; Phone Number: 86-022-23909282; Email: liuhuimin@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital
      • Contact: Dehui Zou, Dr.; Phone Number: 86-022-23909282; Email: zoudehui@ihcams.ac.cn
      • Contact: Huimin Liu, Dr.; Phone Number: 86-022-23909282; Email: liuhuimin@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects must have histological confirmation of relapsed or refractory classic Hodgkin lymphoma (HL).
2. 18 to 65 years of age.
3. Subjects with lymphoma must have at least one measureable lesion >1 cm as defined by lymphoma response criteria.
4. 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%).
5. Eastern Cooperative Oncology Group (ECOG) Performance status 0-2.
6. LVEF value measured by echocardiography ≥50%.
7. Life expectancy > 3 months.

Exclusion Criteria:

1. Patients with central nervous system involvement by lymphoma.
2. 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.
3. Known systemic vasculitides, primary or secondary immunodeficiency(such as HIV infection or severe inflammatory disease).
4. Pregnant or breastfeeding women.
5. Major surgery within 4 weeks before enrollment.
6. 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).
7. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: autologous stem cell transplantation; decitabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	PFS	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	ORR	2 years
Complete response rate	CRR	2 years
Duration of response	DOR	2 years
Overall survival rate	OS	2 years
Severity of the adverse events		2 years

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital
• Investigators: Principal Investigator: Dehui Zou, Dr., Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2022
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: November 16, 2021
• First Posted (Actual): November 30, 2021

Study Record Updates

• Last Update Posted (Actual): December 17, 2021
• Last Update Submitted That Met QC Criteria: December 14, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: relapse; refractory; Hodgkin lymphoma; PD-1 inhibitor; autologous stem cell transplantation; decitabine
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Lymphoma; Hodgkin Disease; Recurrence; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine; Immune Checkpoint Inhibitors
• Other Study ID Numbers: IIT2021051-EC-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No