W-JHS HL01

JRCT ID: jRCTs071200092

Registered date:27/01/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Hodgkin's lymphoma
• Date of first enrollment: 16/03/2021
• Target sample size: 60
• Study type: Interventional

Intervention(s)

1. Administration of adriamycin, vinblastine, dacarbazine and brentuximab vedotin on day 1 and 15 shall be repeated every 28 days. Six cycle s of treatment shall be performed every 28 days as 1 cycle.
2. The starting dose of each drug shall be as follows and the dose should be reduced according to the judgment of the investigator according to the age and symptoms.
Adriamycin: 25 mg/m2, IV or DIV
Vinblastine: 6 mg/m2, IV or DIV
Dacarbazine: 375 mg/m2, DIV (Shading including root at administration)
Brentuximab vedotin: 1.2 mg/kg, DIV
3. Response assessment shall be performed at the end of cycle 2, at the end of treatment completion, at 6months, 1 year, 2 year and at the time point of recurrence after administration completion.

Outcome(s)

• Primary Outcome: Complete Response (CR) rate of A-AVD therapy

Secondary Outcome

1.Therapeutic effect (overall response rate; RR, progression free survival; PFS, overall survival; OS) of A-AVD therapy
2.Enforcement rate of the primary prevention with G-CSF and incidence rate of febrile neutropenia (FN) in patients treated with A-AVD therapy
3.Relative dose intensity (RDI) and response rate of each drug in patients treated with A-AVD therapy
4.Contents and the effect of treatment after recurrence in patients who recurred during study period
5.Safety of A-AVD therapy

Exploratory endpoints:
Evaluation of tumor cell gene mutations and immune microenvironment using samples at the time of diagnosis, correlation with therapeutic effect
MRD assessment using cell free DNA

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients who are newly diagnosed as Ann Arbor classification stage IIB - IV Hodgkin lymphoma, and who are planned to treat with A-AVD therapy as first line therapy.
2) Patients who are >=20 years of age (at time point of the signature of ICF).
3) Patients who diagnosed as classical Hodgkin lymphoma (nodular sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte depletion) according to WHO classification.
4) Patients with measurable target lesion based on Revised Response Criteria for Malignant Lymphoma (Cheson 2007).
5) Patients who understand the informed consent and can sign the informed consent form on their own free will.
6) Patients who obey the protocol visit and other rules.
7) Good Performance status(PS)(0, 1 and 2).
8) Patients who meet the following criteria within 7 days before enrollment (it is eligible if patients meet even once. Also, it is not necessary to meet at the same time, and it is possible to do so on another day.)
1. Absolute neutrophil count : ANC )>= 1,500/ mm3
2. Platelet count >= 75,000/mm3
*1 and 2 are adaptable to only patients without bone marrow infiltration.
3. Total bilirubin <=2.0 mg/dL
4. AST(GOT)<=3 X ULN
5. ALT(GPT)<=3 X ULN
6. Serum creatinine<= 2.0 mg/dL
or calculated creatinine clearance >= 40 mL/min
7. Hb >= 8g/dL
* An adaptation of test results after G-CSF administration or transfusion is also capable.
9) Agree to contraception during the study period (male and female patients).

Exclude criteria

1) Patients with active infection requiring systemic treatment.
2) Female patients who are pregnant, possibly pregnant, within 28 days after birth, or lactating.
3) Patients who have mental illness or psychiatric symptoms and are judged to be difficult to participate in the study.
4) Patients with known cerebral disease or meningeal disease (due to the underlying disease or other causes) including signs and symptoms of PML.
5) Patients with symptomatic neuropathy that cause distress on activities of daily life or need medication.
6) Patients with sensory or motor peripheral neuropathy of grade 2 or higher in CTCAE v 5.0.
7) Patients who are known to have hypersensitivity to recombinant protein, mouse protein, or any of the therapeutic agents in this study.
8) Having active double cancer.
9) Patients with unstable angina or anamnesis of myocardial infarction within 6 months.
10) Patients with grade 3 or more impairment of the liver, heart or kidney in CTCAE v 5.0
11) Patients who have received systemic chemotherapy for Hodgkins lymphoma (however, local radiation therapy is eligible).
12) Patients whose A-AVD therapy is judged inappropriate by investigators.
13) Patients who were judged to be ineligible for the study participation by investigators.

Related Information

• Primary Sponsor: Shibayama Hirohiko
• Source(s) of Monetary Support: Takeda Pharmaceutical Co., Ltd.