Procarbazine Hydrochloride Capsule (Natulan®) Clinical Trial Protocol

1. To observe and compare the overall response rate (ORR) of baseline BEACOPP and ABVD regimens for patients with advanced Hodgkin's lymphoma.
2. To evaluate the safety of Natulan® in Chinese patients with advanced Hodgkin's lymphoma

Study Overview

• Status: Unknown
• Conditions: Advanced Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Natulan; Drug: ABVD

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.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; baseline BEACOPP regimen	Drug: Natulan; 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; Other Names: Procarbazine hydrochloride capsules
Active Comparator: controlled group; ABVD regimen	Drug: ABVD; 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;

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	Time Frame
safety as measured by changes of vital signs, ECG and AE number	45 months

Collaborators and Investigators

• Sponsor: Lee's Pharmaceutical Limited

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: May 24, 2016
• First Submitted That Met QC Criteria: June 10, 2016
• First Posted (Estimate): June 15, 2016

Study Record Updates

• Last Update Posted (Actual): September 4, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Procarbazine
• Other Study ID Numbers: Zhaoke-NTL-2015-01