Avastin+ GemAOD As First-Line Treatment in NK/T Cell Lymphoma

An Open-Label, Uncontrolled, Single Centered Phase Ⅱ Study of Avastin Combined With Gemcitabine, Oxaliplatin, Pegaspargase and Dexamethasone (Avastin+ GemAOD) As First-Line Treatment in Patients With Untreated NK/T Cell Lymphoma

The purpose of this study is to evaluate the efficacy and safety of avastin combined with gemcitabine, oxaliplatin, pegaspargase and dexamethasone(Avastin+ GemAOD) as first-line treatment in patients with untreated natural killer(NK)/T cell lymphoma

Study Overview

• Status: Unknown
• Conditions: Extranodal NK/T-cell Lymphoma, Nasal Type
• Intervention / Treatment: Biological: Avastin; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Pegaspargase; Drug: Dexamethasone

Detailed Description

Recent study showed that vascular endothelial growth factor (VEGF) was associated with a poorer outcome in patients with Non-Hodgkin's Lymphoma,and Avastin impacted on tumor endothelial cells to make standard chemotherapy work better for T cell lymphoma. Many researches on Gemcitabine combined with Oxaliplatin for treatments of recurrent and refractory Non-Hodgkin's lymphoma showed patients could benefit from the combination treatment . Pegaspargase plays an important role for treatment of NK/T cell lymphoma. Dexamethasone is used in combination with other agents for the treatment of lymphomas which may be implicated in the development or growth of some cancers.So we explored to evaluate the efficacy and safety of Avastin combined with gemcitabine, oxaliplatin, pegaspargase and dexamethasone(Avastin+ GemAOD) as first-line treatment in patients with untreated NK/T cell lymphoma

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhiming Li, MD; Phone Number: 86-20-87343765; Email: lizhm@sysucc.org.cn
• Study Contact Backup: Name: Yu Wang, MD; Phone Number: 86-20-87343349; Email: wangyu@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Department of Medical Oncology, Sun Yat-Sen University Cancer Center
      • Contact: Zhiming Li, MD; Phone Number: +86-13719189172; Email: lizhm@sysucc.org.cn
      • Contact: Yu Wang, MD; Phone Number: +86-20-87343765; Email: wangyu@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologic diagnosis of NK/T Cell Lymphoma;
• Age:18-80 years;
• Eastern Cooperative Oncology Group (ECOG) status 0-3, Estimated survival time > 3 months;
• Normal haematological, liver and renal function (WBC count≥4×109/L, Hemoglobin≥100g/L, platelet count≥100×109/L, bilirubin<1.5×ULN, Alanine transaminase (ALT) or Aspartate Aminotransferase (AST)<2.5×ULN, serum creatinine<1.5×ULN), normal coagulation function and cardiac function;
• Appreciable and measurable lesions ;
• No history of other malignancies;
• No previous treatments including chemotherapy, radiotherapy, targeted therapy or stem cell transplantation;
• No other serious diseases which conflict with the treatment in the present trial;
• No concurrent treatments that conflict with the treatments in the present trial(including steroid drugs);
• Voluntary participation and signed the informed consent.

Exclusion Criteria:

• The patients had the conditions below: clinically significant ventricular tachycardia (VT), atrial fibrillation (AF), heart block, myocardial infarction (MI), congestive heart failure (CHF), symptomatic coronary artery heart disease requiring medication;
• The patients suffered from organ transplant
• The patients participated in other clinical trials within the 30 days before enrollment or who are participating in other clinical studies;
• The patients with active bleeding or new thrombotic disease, who are taking anticoagulant drugs or with a history of bleeding tendencies;
• The patients suffered before surgery less than four weeks, or after less than six weeks;
• The patients with major vascular invasion;
• The patients with abnormal liver function (total bilirubin> 1.5 times the normal value, ALT / AST> 2.5 times normal), abnormal renal function (serum creatinine> 1.5 times normal), blood abnormalities (absolute neutrophil count <1.5 × 109 / L, platelets <80 × 109 / L, hemoglobin <90g /L) ;
• The patients with moderate to severe proteinuria;
• Severe hypertension,BP≥160/100mmHg;
• The patients with mentally ill / unable to obtain informed consent;
• The patients with drug addiction, alcohol abuse which affects the long-term evaluation of test results;
• The patients in pregnancy, lactation and women of childbearing age who do not want to take contraceptive measures subjects;
• Clinical and laboratory support brain metastases;
• The patients with a history of allergy to test drug;
• The patients not suitable to participate in the investigator judged by researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avastin+ GemAOD; Avastin+ GemAOD means Avastin Combined With Gemcitabine, Oxaliplatin, Pegaspargase and Dexamethasone	Biological: Avastin; Avastin 7.5mg/Kg, intravenous drip D1; Drug: Gemcitabine; Gemcitabine 1g/m2 intravenous drip D1,D8; Drug: Oxaliplatin; Oxaliplatin 130mg/m2 intravenous drip D1; Drug: Pegaspargase; Pegaspargase 2500U/m2 intramuscular injection (IM) D1; Drug: Dexamethasone; Dexamethasone 20mg/d intravenous drip D1, po D2-3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate(ORR)	21 days(3 weeks) for one cycle,Efficacy was evaluated every two cycles	every 6 weeks,up to completion of treatment(approximately 6 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progress Free Survival(PFS)		up to end of follow-up-phase (approximately 5 years)
Overall Survival(OS)		up to the date of death (approximately 5 years)
The tolerance and the side effects of the treatment	21 days(3 weeks) for one cycle,Toxicity was evaluated every cycle	every 3 weeks,up to completion of treatment(approximately 6 months)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epstein-Barr virus(EBV) DNA copies	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
lymphocyte count	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
Monocyte Count	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
C reactive protein	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
Plasma β2-microglobulin	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)
Urinary microglobulin β2	21 days(3 weeks) for one cycle	every 3 weeks,up to completion of treatment(approximately 6 months)

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Eli Lilly and Company; Hoffmann-La Roche
• Investigators: Principal Investigator: Wenqi Jiang, MD, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China; Principal Investigator: Zhiming Li, MD, Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Anticipated): August 1, 2015
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: August 3, 2013
• First Submitted That Met QC Criteria: August 12, 2013
• First Posted (Estimate): August 13, 2013

Study Record Updates

• Last Update Posted (Estimate): August 22, 2013
• Last Update Submitted That Met QC Criteria: August 20, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: first line chemotherapy; NK/T-cell Lymphoma; Avastin+ GemAOD
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Extranodal NK-T-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Gemcitabine; Dexamethasone; Oxaliplatin; Bevacizumab; Pegaspargase
• Other Study ID Numbers: B2013-017-01