Efficacy and Safety of CDOP vs CHOP for Newly Diagnosed Peripheral T-cell Lymphoma

Study Overview
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Brief Summary
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Primary objective of the study is to compare the efficacy and safety of CDOP versus CHOP for newly diagnosed peripheral T-cell lymphoma (PTCL).

Detailed Description
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This is a open-label, multi-center, randomized, non-inferiority study to compare efficacy and safety of CDOP with standard CHOP regimen in patients with previously untreated PTCL. Study subjects are patients with histologically proven newly diagnosed PTCL. Patients are randomized 1:1 to receive either cyclophosphamide, pegylated liposomal doxorubicin, vincristine and prednisone (CDOP) administered in 3 week cycles for 6 cycles or cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles.This study is divided into three phases: screening phase, treatment phase and follow-up phase. Patients will receive study drug(s) for up to 6 cycles, or until unacceptable toxicity will develop or progression or voluntary withdrawal.Adverse event of every treatment cycle will be recorded.Therapy efficacy will be evaluated after finishing 2 cycles, 4cycles and finishing 6 cycles therapy. Patients will be followed until disease progression, died or 2 years from the last patient randomized.

Official Title
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Open-label Multi-center Randomized Non-inferiority Study to Compare Efficacy and Safety of Pegylated Liposomal Doxorubicin Versus Doxorubicin for Newly Diagnosed Peripheral T-cell Lymphoma

Conditions
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Peripheral T-cell Lymphoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: pegylated liposomal doxorubicin
* Drug: Vincristine
* Drug: Prednisone
* Drug: Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically proven untreated peripheral T-cell lymphoma (include PTCL not otherwise specified（PTCL-NOS）, angioimmunoblastic T cell lymphoma（AITL）, anaplastic large cell lymphoma（ALCL）and other peripheral T-cell lymphoma(except NK/T cell lymphoma); Males and females of 18 years of age to 75 years of age. Eastern Cooperative Oncology Group (ECOG) performance status 0- 2. At least 1 single size measurable lesions, CT or PET-CT scan shows more than 15mm. Estimated survival time ≥ 6 months Liver function: transaminases≤3×ULN，or transaminases≤3×ULN for liver metastasis，total bilirubin ≤1.5ULN，or total bilirubin ≤2.5ULN for Gilbert's syndrome Renal function: serum creatinine ≤1.5×ULN or creatinine clearance ≥ 60 ml / min ( standard Cockcroft-Gault formula); peripheral hemogram: WBC≥3.0×10^9/L, ANC≥1.5×10^9/L, Hb≥90g/L, PLT≥75×10^12/L. Cardiac ultrasound LVEF≥55%; New York Heart Association (NYHA) heart function classification is I grade; sign informed consent. Exclusion Criteria: Patients with primary or secondary central nervous system lymphoma； Serious heart disease, including but not limited to: 1)Significant ventricular arrhythmia or high degree atrioventricular block (Mobitz II or third degree atrioventricular block); 2) unstable angina; 3) clinically significant heart valve disease; 4) Electrocardiogram shows transmural myocardial infarction; 5) Uncontrollable hypertension; 3. interstitial pneumonia, allergic asthma or severe allergic medical history; 4.Patients with other malignancies in the past or now (except basal cell carcinoma, squamous-cell carcinoma or carcinoma in situs of cervix that has been adequately treated), 5.HIV antibody positivity; 6.Acute or chronic active hepatitis B (HBsAg positivity, HBV DNA negative acceptable), acute or chronic active hepatitis C (HCV antibody negatively acceptable; HCV antibody positivity, HCV RNA negative acceptable) 7.Pregnancy or lactation period 8.Patients with Organ transplantation 9.Patients with serious uncontroled acute infection 10.High doses of hormones are contraindicated, such as uncontrolled hyperglycemia, stomach ulcers or Mental illness, etc. 11.Patients with severe neurological or psychiatric history, including dementia or epilepsy 12.The researchers considered that patients are not suitable for the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CDOP regimen<br>cyclophosphamide, pegylated liposomal doxorubicin, vincristine and prednisone (CDOP) administered in 3 week cycles for 6 cycles. | Drug: Cyclophosphamide<br>* 750mg/m² ivgtt on day 1<br>* Other names: CTX;Drug: pegylated liposomal doxorubicin<br>* 40mg/m² ivgtt on day 1<br>* Other names: PLD;Drug: Vincristine<br>* 1.4mg/m²(Maximum 2 mg) ivgtt on day 1<br>* Other names: VCR;Drug: Prednisone<br>* Prednisone100mg/m² po on day1-5<br>* Other names: PED;|
| Active Comparator: CHOP regimen<br>cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) administered in 3 week cycles for 6 cycles. | Drug: Cyclophosphamide<br>* 750mg/m² ivgtt on day 1<br>* Other names: CTX;Drug: Vincristine<br>* 1.4mg/m²(Maximum 2 mg) ivgtt on day 1<br>* Other names: VCR;Drug: Prednisone<br>* Prednisone100mg/m² po on day1-5<br>* Other names: PED;Drug: Doxorubicin<br>* 50mg/m² ivgtt on day 1<br>* Other names: DOX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | complete response (CR) and partial response (PR) rates, using the standard response criteria | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | from date of inclusion to date of progression, relapse, or death from any cause | 2 years | 
| Overall Survival | from the date of inclusion to date of death, irrespective of cause | 2 years | 
| Cardiac toxicity | cardiotoxity Congestive heart failure with clinical symptoms, or no symptoms but an abnormal LVEF | 2 years | 
| Adverse Events | any unfavorable and unintended sign , symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure | 2 years |