PD-1 Inhibitor or PD-1 Inhibitor Plus GVD for Relapsed/Refractory CHL

PD-1 Inhibitor or PD-1 Inhibitor Plus GVD(Gemcitabine, Vinorelbine and Doxorubicin Liposome) Regimen for Relapsed/Refractory Classical Hodgkin Lymphoma (R/R CHL): a Single Arm, Open Label, Phase II Study

This phase 2 trial studies the efficacy and safety of PD-1 inhibitor monotherapy or PD-1 inhibitor with GVD (Gemcitabine, Vinorelbine and Doxorubicin Liposome) regimen for relapsed or refractory classical Hodgkin lymphoma (CHL) patients who failed the first-line induction therapy.

Study Overview

• Status: Recruiting
• Conditions: Classical Hodgkin Lymphoma; Refractory or Relapsed Classical Hodgkin Lymphoma
• Intervention / Treatment: Drug: PD-1 inhibitor; Drug: PD-1 inhibitor, gemcitabine, vinorelbine and doxorubicin liposome

• Study Type: Interventional
• Enrollment (Anticipated): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • The First Affiliated Hospital of Guangdong Pharmaceutical University
    • Guangzhou, Guangdong, China, 51000
      • Recruiting
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically confirmed classical Hodgkin lymphoma;
• Refractory to or relapsed after first-line induction therapy; prior radiotherapy is allowed;
• At least one evaluable lesion according to 2014 Lugano criteria;
• Life expectancy > 3 months;
• Eastern Cooperative Oncology Group (ECOG) of 0-1;
• Able to participate in all required study procedures;
• Proper functioning of the major organs: 1) The absolute value of neutrophils (>1.5×10^9/L); 2) platelet count (> 75×10^9/L); 3) Hemoglobin (> 80 g/L); 4) Serum creatinine <1.5 times Upper Limit Normal (ULN) ; 5) Serum total bilirubin < 1.5 times ULN; 6) Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) < 2.5 times ULN; 7) Coagulation function: International Normalized Ratio (INR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) < 1.5 times ULN (unless the subject is receiving anticoagulant therapy and PT and APTT are within the expected range at screening time). ; 8) Thyrotropin (TSH) or free thyroxine (FT4) or free triiodothyronine (FT3) were all within the normal range (±10%);
• There was no evidence that subjects had difficulty breathing at rest, and the measured value of pulse oximetry at rest was more than 92%;
• Volunteers who signed informed consent.

Exclusion Criteria:

• Involvement of central nervous system (CNS);
• Previously received treatment of immune checkpoint inhibitors (eg. PD-1, PD-L1, CTLA-4);
• Previously received treatment of hematopoietic cell transplantation;
• Patients with Hemophagocytic syndrome;
• 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;
• Requiring treatment with corticosteroids or other immunosuppressive drugs within 14 days of study drug administration [allowing subjects to use local, ocular, intra-articular, intranasal and inhaled glucocorticoid therapy (with very low systemic absorption); and allowing short-term (< 7 days) glucocorticoid prophylaxis (e.g., contrast agent overdose sensitivity) or for the treatment of non-autoimmune diseases (e.g. delayed hypersensitivity caused by contact allergens).
• Uncontrolled active infection, with the exception of tumor-related B symptom fever;
• History of human immunodeficiency virus (HIV) infection and/or patients with acquired immunodeficiency syndrome are known;
• Patients with active hepatitis B or active hepatitis C. Patients who are positive for hepatitis B Surface Antigen (HBsAg) or hepatitis C Virus (HCV) antibodies at screening stage must pass further detection of hepatitis B Virus (HBV) DNA (no more than 10^4 copies/mL) and HCV RNA (no more than the lower limit of the detection method) in the row. Hepatitis B carriers, stable hepatitis B (DNA titer should not be higher than 10^4 copies/mL) after drug treatment, and cured hepatitis C patients can be enrolled in the group;
• Diagnosed with or receiving treatment for malignancy other than lymphoma;
• Pregnant or breastfeeding women;
• Other researchers consider it unsuitable for patients to participate in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: PD-1 Inhibitor or PD-1 Inhibitor with GVD; All patients receive PD-1 Inhibitor on day 1. Treatment cycles repeat every 3 weeks for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients with PET/CT confirmed CR or PR receive PD-1 Inhibitor for another 3 cycles. Patients with PD or SD receive PD-1 Inhibitor plus GVD (gemcitabine, vinorelbine and doxorubicin liposome) regimen every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with PET/CT confirmed CR after 6 cycles of PD-1 Inhibitor treatment can receive radiotherapy or ASCT, which is determined by investigators. Patients with PR receive 2-4 cycles of PD-1 Inhibitor plus GVD regimen. Patients with PD or SD receive 4 cycles of PD-1 Inhibitor plus GVD regimen. Patients with confirmed CR or PR after PD-1 Inhibitor plus GVD regimen can receive radiotherapy or ASCT, which is determined by investigators. Patients with PD or SD quit the trial.

Drug: PD-1 inhibitor; PD-1 Inhibitor, intravenous drip, d1.; Drug: PD-1 inhibitor, gemcitabine, vinorelbine and doxorubicin liposome; PD-1 Inhibitor, intravenous drip, d1; Gemcitabine, 1000mg/m2, intravenous drip, d1,d8; Vinorelbine, 50mg/m2, PO, d1,d8; Doxorubicin Liposome, 30mg/m2, intravenous drip, d1;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate	Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	The time from the start of treatment to the progression of the tumor or death (due to any cause).	5 years
Overall Survival	The time from the start of treatment to time of death (due to any cause).	5 years
Duration of Response	The time from the first assessment of complete remission or partial remission to progressive disease or death (due to any cause).	5 years
Objective Response rate	Objective Response rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.	2 years
Time to Response (TTR)	The time from the start of treatment to the first assessment of complete remission or partial remission.	2 years
Percentage of Participants With Adverse Events	Adverse Events will be determined and graded on the basis of investigator assessments according to NCI CTC AE 5.0	2 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2021
• Primary Completion (ANTICIPATED): April 1, 2025
• Study Completion (ANTICIPATED): April 1, 2025

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (ACTUAL): November 12, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Gemcitabine; Doxorubicin; Liposomal doxorubicin; Vinorelbine; Immune Checkpoint Inhibitors
• Other Study ID Numbers: B2020-238-01

Drug and device information, study documents

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