Clinical Application of Polyethylene Glycol Liposome Doxorubicin (PLD) in Primary Lymphoma

Study Overview
=================
Brief Summary
-----------------
Anthracyclines were basic drugs in lymphoma treatment. However, their dose accumulation related cardiac toxicity limits their clinical application, especially adriamycin. Adriamycin has been gradually replaced by epirubicin. Polyethylene glycol liposome doxorubicin (PLD) can go into tumor tissues through tumor angiogenesis and produces targeted killing effect to tumor tissues. PLD has potential advantages in the treatment of malignant tumors,including lymphoma.

Detailed Description
-----------------
Lymphoma is one of the most rapidly growing malignant tumors in the world. It was divided into two major categories (Hodgkin's lymphoma (HL) and non Hodgkin's lymphoma (NHL). Anthracyclines were basic drugs in lymphoma treatment. However, their dose accumulation related cardiac toxicity limits their clinical application, especially adriamycin. Adriamycin has been gradually replaced by epirubicin in malignant tumor treatment because of its similar effects and less toxic side effects. Polyethylene glycol liposome doxorubicin (PLD) is the liposome formulation of doxorubicin. Methoxy Polyethylene Glycol (MPEG) contained in liposome surface can decrease the peak plasma levels of free drugs, extend drugs circulation time in blood and reduce the chance of non-specific distribution to normal tissues. PLD goes into tumor tissues through tumor angiogenesis and produces targeted killing effect to tumor tissues. PLD has potential advantages in the treatment of malignant tumors. In lymphoma patients' therapy, the clinical application of PLD is expected to be a new method. Therefore, the investigators designed the randomized controlled clinical study and aimed to compare the efficacy and safety between PLD and epirubicin in primary B-NHL, peripheral T-cell lymphoma (PTCL) and HL patients.

Official Title
-----------------
Clinical Application of Polyethylene Glycol Liposome Doxorubicin (PLD) in Primary Lymphoma

Conditions
-----------------
Lymphoma, Non-Hodgkin;Hodgkin Disease

Intervention / Treatment
-----------------
* Drug: R-CHOP/CHOPE or ABVD chemotherapy regimen
* Drug: R-CDOP/CDOPE or DBVD chemotherapy regimen


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Primary B-NHL, PTCL (ALK+ anaplastic large cell lymphoma and NK(natural killer cell )/T cell lymphoma were excluded) or HL patients confirmed by histopathology; Ages ≥18 years old, < 80 years old; ECOG (Eastern Cooperative Oncology Group）score: 0-2 At least one measurable lesion; Expected survival time≥3 months; Liver function: transaminase≤2.5× upper limit of normal value，bilirubin≤1.5×upper limit of normal value; Renal function: serum creatinine is 44-133 mmol/L; Routine blood test：WBC≥3.0×109/L，Neutrophils≥1.5×109/L，Hb≥100g/L，Platelet≥80×109/L； LVEF≥50%; New York Heart Association (NYHA) heart function classification is I-II grade signed informed consent. Exclusion Criteria: Patients with severe complications or severe infection; Invasion of central nervous system; Patients with severe heart disease history, including ventricular tachycardia (VT), atrial fibrillation (AF), heart block, myocardial infarction (MI), congestive heart failure (CHF), coronary heart disease patients needed therapy; patients with severe allergic constitution, or those who are allergic to or intolerant of drug composition in chemotherapy regimens; with other malignant tumors in the past 5 years; patients received doxorubicin therapy, total cumulative dose of adriamycin was more than 300 mg/m2, total cumulative dose of epirubicin was more than 450 mg/m2; Patients participate in other clinical studies; Other patients who are not suitable for the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: R-CHOP/CHOPE or ABVD chemotherapy regimen<br>R-CHOP/CHOPE every 21 days or ABVD every 28 days for total 6 courses | Drug: R-CHOP/CHOPE or ABVD chemotherapy regimen<br>* R-CHOP: Rituximab：375mg/m2，ivgtt，D0； Epirubicin：70 mg/m2，ivgtt，D1 ； Cyclophosphamide：750 mg/m2，ivgtt，D1； Vincristine: 1.4 mg/m2 ivgtt，D1 ； Prednison：100mg/d，po，D1-5； CHOPE: Epirubicin：70 mg/m2，ivgtt，D1 ； Cyclophosphamide：750 mg/m2，ivgtt，D1； Vincristine: 1.4 mg/m2 ivgtt，D1 ； Prednison：100mg/d，po，D1-5； Etoposide: 100 mg/（m2•d），ivgtt，D1-3; ABVD: Epirubicin：35 mg/m2，ivgtt，D1、15； Bleomycin：10 mg/m2，ivgtt，D1、15； Vincristine：1.4 mg/m2，ivgtt，D1、15； Dacarbazine：375mg/m2，ivgtt，D1、15；<br>|
| Experimental: R-CDOP/CDOPE or DBVD chemotherapy regimen<br>R-CDOP/CDOPE every 21 days or DBVD every 28 days for total 6 courses | Drug: R-CDOP/CDOPE or DBVD chemotherapy regimen<br>* R-CDOP: Rituximab：375mg/m2，ivgtt，D0； PLD 30-40 mg/m2，ivgtt，D1 ； Cyclophosphamide：750 mg/m2，ivgtt，D1； Vincristine: 1.4 mg/m2 ivgtt，D1 ； Prednison：100mg/d，po，D1-5； CDOPE: PLD 30-40 mg/m2，ivgtt，D1； Cyclophosphamide：750 mg/m2，ivgtt，D1； Vincristine: 1.4 mg/m2 ivgtt，D1 ； Prednison：100mg/d，po，D1-5； Etoposide: 100 mg/（m2•d），ivgtt，D1-3; DBVD: PLD 15-20 mg/m2，ivgtt，D1； Bleomycin：10 mg/m2，ivgtt，D1、15； Vincristine：1.4 mg/m2，ivgtt，D1、15； Dacarbazine：375mg/m2，ivgtt，D1、15；<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with complete remission （CR） | Sum of products of greatest diameters （SPD）was used to evaluate the therapy effect.Number of participants with CR was assessed by Cheson Standard. | After two 21-day or 28-day courses, up to 42 to 56 days. |