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

• ClinicalTrials.gov Identifier: NCT04843267
• Recruitment Status: Recruiting
• First Posted: April 13, 2021
• Last Update Posted: April 13, 2021
• Sponsor: Sun Yat-sen University
• Information provided by (Responsible Party): Li Zhiming, Sun Yat-sen University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Hodgkin Lymphoma; Chemotherapy Effect	Drug: Tislelizumab	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Estimated Study Start Date: May 1, 2021
• Estimated Primary Completion Date: May 1, 2023
• Estimated Study Completion Date: May 1, 2025

Arms and Interventions

Intervention Details:

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

Outcome Measures

Primary Outcome Measures :

1. complete response rate after two cycles of tislelizumab [ Time Frame: 6 weeks ]
   complete response rate after two cycles of tislelizumab by PET/CT

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

China, Guangdong

Sun Yat-Sen University Cancer Center; Recruiting

Guangzhou, Guangdong, China, 510000

Contact: Zhiming Li +86-020-87343765 lizhm@sysucc.org.cn

Sponsors and Collaborators

Sun Yat-sen University

More Information

• Responsible Party: Li Zhiming, Professor, Sun Yat-sen University
• ClinicalTrials.gov Identifier: NCT04843267
• Other Study ID Numbers: B2020-324-01
• First Posted: April 13, 2021
• Last Update Posted: April 13, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases