Procarbazine Hydrochloride Capsule (Natulan®) Clinical Trial Protocol

Study Overview
=================
Brief Summary
-----------------
To observe and compare the overall response rate (ORR) of baseline BEACOPP and ABVD regimens for patients with advanced Hodgkin's lymphoma. To evaluate the safety of Natulan® in Chinese patients with advanced Hodgkin's lymphoma

Detailed Description
-----------------
This is a confirmatory open-label, randomized, controlled, multicenter study. Recruited subjects are to be randomized to treatment group and controlled group, with ratio of 1:1. Treatment group will accept baseline BEACOPP regimen, while controlled group will accept ABVD regimen. The study design consisted of a screening phase of 1 week, a treatment phase of 24 or 32 weeks, and a post treatment follow-up of at least 2 years.

Conditions
-----------------
Advanced Hodgkin's Lymphoma

Intervention / Treatment
-----------------
* Drug: Natulan
* Drug: ABVD


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject is of age 18 65, both male and female; Newly pathologically diagnosed with classical Hodgkin's lymphoma (lymphocyte depletion type, lymphocyte rich type, nodular sclerosing type, and mixed cellularity type), who had not accepted previous treatment; Had stage IIB, III or IV disease, as assessed by the Ann Arbor classification; ECOG≤2, life expectancy ≥3 month; A negative serum pregnancy test required for sexually active women of childbearing potential; The subject voluntarily gives written informed consent to participate in the study. Exclusion Criteria: Hematopoietic function: Leukocyte <3,500/mm3（3.5×109/L） Neutrophils <1,500/mm3（1.5×109/L） Platelets <100,000/mm3（100×109/L） Intolerance to any of the active ingredients and/or excipients in the study medications; Severe central nervous system disorders and mental illness; Severe heart disease (congestive heart failure, uncontrolled hypertension, unstable coronary artery disease, or myocardial infarction, or severe arrhythmia). Echocardiography showed resting left ventricular ejection fraction (LVEF) < 50%); History of severe lung disease; AST or ALT>2.5×ULN，total bilirubin≥1.5×ULN，serum creatinine>1.5×ULN (for subject with liver metastases: AST or ALT>5xULN, total bilirubin ≥ 3xULN); Uncontrolled, systemic, active infection； Positive serology to HIV; HBsAg positive subjects can still be enrolled in the study, but researchers should follow The consensus on the Treatment of Lymphoma with Hepatitis B Infections to observe closely and/or provide prophylactic anti-HBV therapy (as per investigator's decision); Other previous or concomitant malignancy, except for basal cell carcinoma and/or cervical carcinoma in situ; The subject is receiving an investigational drug, or has participated in an investigational study within 30 days prior to screening; The subject is pregnant or lactating; or subjects of childbearing potential (both women and man subjects) do not want to take effective contraceptive measures during study period or within 3 months after study completes; Investigators believe subjects not suitable to participate in the study for other reasons.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>baseline BEACOPP regimen | Drug: Natulan<br>* Each baseline BEACOPP regimen lasts 21 days, and each cycle consists of： Cyclophosphamide injection: 650mg/m2, IV infusion, day 1； Doxorubicin hydrochloride injection: 25mg/m2, IV infusion, day 1； Etoposide injection: 100mg/m2, IV infusion, day 1 3; Natulan (procarbazine hydrochloride capsule): 100mg/m2，po, day 1 7; Bleomycin hydrochloride injection: 10mg/m2, IV or IM, day 8; Vincristine: 1.4mg/m2 (single maximum dose is 2mg), IV infusion, day 8; Prednisone tablet: 40mg/m2, po, day 1 14<br>* Other names: Procarbazine hydrochloride capsules;|
| Active Comparator: controlled group<br>ABVD regimen | Drug: ABVD<br>* Each ABVD cycle lasts 28 days1 cycle of the ABVD regimen consists of： Doxorubicin hydrochloride injection：25mg/m2，IV infusion，day 1 and 15; Dacarbazine injection：375mg/m2，IV infusion，day 1 and 15； Bleomycin injection：10mg/m2，IV or IM，day 1 and 15； Vincristine injection：1.4mg/m2 (single maximum dose is 2mg), IV infusion，day 1 and 15;<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate (ORR) | Compare the overall response rate (ORR) of baseline BEACOPP and ABVD regimens for in patients with advanced Hodgkin's lymphoma. | 45 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety as measured by changes of vital signs, ECG and AE number |  | 45 months |