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

Sponsor

Sun Yat-sen University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04624984

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Classical Hodgkin Lymphoma Refractory or Relapsed Classical Hodgkin Lymphoma	Drug: PD-1 inhibitor Drug: PD-1 inhibitor, gemcitabine, vinorelbine and doxorubicin liposome	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 1, 2021

Anticipated Primary Completion Date :

Apr 1, 2025

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

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;

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;

Outcome Measures

Primary Outcome Measures

Complete remission rate [2 years]
Complete remission rate will be determined on the basis of investigator assessments according to 2014 Lugano criteria.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University,	Guangzhou	Guangdong	China	51000
2	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510060
3	The First Affiliated Hospital of Guangdong Pharmaceutical University	Guangzhou	Guangdong	China	510060