A Multi-center, Non-randomized, Open-label Phase II Clinical Study on the Treatment of Newly Diagnosed Advanced Hodgkin's Lymphoma With PD-1 Antibody (Tislelizumab) Combined With AVD Regimen (Doxorubicin, Vindesine, Dacarbazine) Under the Guidance of PET/CT

Hodgkin Lymphoma Clinical Trial

Official title:

A Multi-center, Non-randomized, Open-label Phase II Clinical Study on the Treatment of Newly Diagnosed Advanced Hodgkin's Lymphoma With PD-1 Antibody (Tislelizumab) Combined With AVD Regimen (Doxorubicin, Vindesine, Dacarbazine) Under the Guidance of PET/CT

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04843267
• Other study ID #: B2020-324-01
• Status: Recruiting
• Phase: Phase 2
• Start date: May 1, 2021
• Est. completion date: May 1, 2025

Study information

• Verified date: April 2021
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The experimental drug regimen in this study includes a PD-1 antibody (tislelizumab) single-drug induction treatment period and a PD-1 antibody + AVD combined treatment period.

1. PD-1 antibody (tislelizumab) single-drug induction treatment period (first 2 courses for all patients + 3-6 courses for CR patients):

PD-1 antibody (tislelizumab), specification: 100mg/bottle. Usage and dosage: intravenous drip, 200mg each time, QD, D1. In the above PD-1 antibody single-drug regimen, 21 days are regarded as a treatment cycle, and all patients first receive 2 courses of PD-1 antibody single-drug induction treatment;

2. PET/CT mid-term efficacy evaluation used for guiding follow-up treatment options:

PET/CT efficacy evaluation before the 3rd course of treatment (PET/CT2):

CR patients: continue to receive PD-1 antibody monotherapy, and then receive 4 courses of PD-1 antibody therapy; PR patients: sequential 4 courses of PD-1 antibody + AVD combined chemotherapy; PD+SD patients: out group, and receive other anti-lymphoma therapy deemed suitable by the investigators;

After the 6th course, patients not out of the group receive PET/CT3 efficacy evaluation:

CR patients: end the treatment and enter the follow-up; PR patients: receive 2 more courses of PD-1 antibody + AVD combined chemotherapy, and then enter the follow-up.

3. PD-1 antibody + AVD combined treatment period (3rd-6th/8th course for PR patients):

PD-1 antibody, specification: 100mg/bottle. Usage and dosage: intravenous drip, 100mg each time, QD, d1, d15. AVD regimen Doxorubicin 25mg/m2, d1, d15 intravenous injection Vindesine 3mg/m2, d1, d15 intravenous injection Dacarbazine 0.375mg/m2, d1, d15 intravenous drip In this combined treatment regimen, every 28 days is a treatment cycle, and the PD-1 antibody is used in combination with AVD in D1 and D15 of each treatment cycle.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Patients with newly diagnosed classical Hodgkin lymphoma (HL) confirmed by histopathology;

2. Stage III-IV, or Stage IIB patients with at least one high-risk factor (NCCN standard)

3. Patients not suitable for receiving radiotherapy subsequently

4. Patients with at least one assessable lesion (according to Lugano 2014 standard);

5. Age 18 or above (including 18), no gender requirement;

6. ECOG PS score of 0-1 points;

7. Expected survival time = 3 months;

8. Hematopoietic function: absolute neutrophil count = 1.5×109/L, platelets = 90×109/L, hemoglobin = 90g/L; liver function: for patients with non-hepatitis B, total bilirubin, ALT and AST <1.5×ULN (upper limit of normal); patients with hepatitis B need to take effective antiviral drugs, and HBV-DNA copy <2000 IU/ml and ALT<2×ULN; renal function: creatinine <1.5×ULN and creatinine clearance rate =50ml/min;

9. With normal main indicators of cardio-pulmonary function, and no obvious contraindication to chemotherapy;

10. Not received any anti-tumor therapy such as radiotherapy, chemotherapy, targeted therapy, cellular immunotherapy or hematopoietic stem cell transplantation before enrollment;

11. Voluntarily signing an informed consent form before trial screening.

Exclusion Criteria:

1. Nodular lymphocyte predominant HL;

2. Patients received any form of anti-tumor therapy in the past;

3. Patients planning to receive radiotherapy or autologous stem cell transplantation;

4. With involvement of central nervous system (meninges or brain parenchyma);

5. Pregnant and lactating women and child-bearing patients who are unwilling to take contraceptive measures;

6. Patients with history of other tumors, except for cured cervical cancer orskin basal cell carcinoma; patients who have received organ transplantation;

7. Patients who have received symptomatic treatment of myelosuppressive toxicity within 7 days before enrollment;

8. Patients who have used any immunosuppressive drugs within 4 weeks before the first-dose treatment,

9. Patients with known active interstitial pneumonia;

10. Abnormal liver function (total bilirubin>1.5×ULN, ALT/AST>2.5×ULN or ALT/AST>5×ULN for patients with liver invasion), abnormal renal function (serum creatinine>1.5×ULN), abnormal electrolyte metabolism;

11. Peripheral neuropathy = Grade 2;

12. Patients with a history of prolonged QT interval which is of clinical significance (male> 450ms, female> 470ms), ventricular tachycardia (VT), atrial fibrillation (AF), heart block, myocardial infarction (MI) within 1 year, congestive heart failure (CHF), patients with symptomatic coronary heart disease requiring drug therapy;

13. Patients with the end-diastolic width of fluid sonolucent area in pericardial cavity =10mm by cardiac B-ultrasonography;

14. Mentally disturbed/patients unable to give informed consent;

15. Patients who affect the evaluation of test results due to drug abuse or long-term alcohol abuse;

16. Participating in another interventional clinical study at the same time; Patients not suitable to participate in this trial by the judgment of investigators.

Related Conditions & MeSH terms

• Chemotherapy Effect
• Hodgkin Disease
• Hodgkin Lymphoma
• Lymphoma

Intervention

Drug:
• Tislelizumab
Tislelizumab in first-line treatment of Hodgkin's lymphoma

Locations

Country	Name	City	State
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	complete response rate after two cycles of tislelizumab	complete response rate after two cycles of tislelizumab by PET/CT	6 weeks