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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Classical Hodgkin Lymphoma, Refractory or Relapsed Classical Hodgkin Lymphoma

Intervention / Treatment
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* Drug: PD-1 inhibitor
* Drug: PD-1 inhibitor, gemcitabine, vinorelbine and doxorubicin liposome


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD-1 Inhibitor or PD-1 Inhibitor with GVD<br>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<br>* PD-1 Inhibitor, intravenous drip, d1.<br>Drug: PD-1 inhibitor, gemcitabine, vinorelbine and doxorubicin liposome<br>* 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;<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| Objective Response rate | Objective Response rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria. | 2 years | 
| 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 | 
| 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 |