PEG-ASP+Gemox Regimen and Thalidomide for NK/T Lymphoma

PA-Gemox Regimen Followed by Thalidomide Versus AspaMetDex Regimen in NKTCL Patients：a Randomized, Open-label, Phase 3 Study

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive form of non-Hodgkin's lymphoma and shows extremely poor survival. This prospective pilot study to evaluate the efficacy and safety of long-acting aspargase (pegylated aspargase, PEG-ASP) combined with gemcitabine and oxaliplatin (PASP -Gemox) treatment in this population.

Study Overview

• Status: Recruiting
• Conditions: Extranodal NK-T-Cell Lymphoma, Nasal and Nasal-Type
• Intervention / Treatment: Drug: pegaspargase; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Thalidomide; Drug: Methotrexate; Drug: Dexamethasone

Detailed Description

Eligibility criteria The eligibility criteria were pathologically confirmed, previously untreated or refractory/relapsed ENKTL as defined by the World Health Organization classification; age≥18 years; Eastern Cooperative Oncology Group (ECOG) performance status of 0-2; at least one measurable lesion; adequate haematologic function (haemoglobin > 9.0 g/l, absolute neutrophil count > 1500/ml, platelets > 75,000/l), hepatic function (total serum bilirubin ≤ 1.5 times the upper limit of normal, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal), renal function (serum creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 50 ml/min); normal coagulation function and electrocardiogram results. Prior chemotherapy and radiotherapy should have been completed >4 weeks earlier, willingness to provide written informed consent. Stage was defined according to the Ann Arbor system. The Sun Yat-Sen University Cancer Centre Research Ethics Board approved this study before subjects were enrolled.

Treatment PA-Gemox dosages were as follows: days 1 and 8, 30-min intravenous infusion of 1000 mg/m2 gemcitabine; day 1, 2-h intravenous infusion of 130 mg/m2 oxaliplatin; day 1, deep intramuscular injection of 2500 U/m2 PEG-ASP at two different sites. The regimen was repeated every 3 weeks for a maximum of six cycles. Stage IE/IIE patients underwent four cycles induction chemotherapy, followed by involved-field radiotherapy after got CR, PR or SD. Three-dimensional conformal radiotherapy was done by linear accelerator at 2.0 grays (Gy) per daily fraction with 5-6 weeks. The involved- field radiation (IFRT) dose was 50-56 Gy. Refractory/relapsed patients underwent at least two cycles treatments unless there was disease progression or unacceptable side effects, or withdrawal of patient consent. Autologous haematopoietic stem cell transplantation (AHSCT) was recommended after they achieved CR.

• Study Type: Interventional
• Enrollment (Anticipated): 264
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Department of Medical Oncology, Sun Yat-sen University Cancer Center,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. pathologically confirmed, previously untreated or refractory/relapsed ENKTL as defined by the World Health Organization classification;
2. age≥18 years;
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
4. at least one measurable lesion;
5. adequate haematologic function (haemoglobin > 9.0 g/l, absolute neutrophil count > 1500/ml, platelets > 75,000/l),
6. adequate hepatic function (total serum bilirubin ≤ 1.5 times the upper limit of normal, alanine aminotransferase and aspartate aminotransferase ≤ 2.5 times the upper limit of normal),
7. adequate renal function (serum creatinine ≤ 1.5 mg/dl, creatinine clearance ≥ 50 ml/min);
8. normal coagulation function and electrocardiogram results.
9. Prior chemotherapy and radiotherapy should have been completed >4 weeks earlier,
10. willingness to provide written informed consent.

Exclusion Criteria:

-

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: PEG-ASP+Gemox regimen group; PEG-ASP 2000U/m2 im d1 Gemcitabine 800mg/m2 ivdrip 30min d1，8 Oxaliplatin 100mg/m2 ivdrip d1 Thalidomide 150-200mg po qn d8-21	Drug: pegaspargase; pegaspargase: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.; Other Names: Oncaspar; Drug: Gemcitabine; 1000mg/m2, ivd on day 1 and 8 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.; Other Names: Gemzar; Drug: Oxaliplatin; 100mg/m2 ivd on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops; Other Names: Eloxatin; Drug: Thalidomide; 100-200mg, PO, after chemotherapy
Active Comparator: AspaMetDex regimen group; Pegaspargase 2000U/m2 im， d1 methotrexate 3000m g/m2 civ 6-hour，d1, Calcium folinate 30mg iv q6h x6 Dexamethasone 40 mg ivdrip QD	Drug: pegaspargase; pegaspargase: 2000U/m2 im on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.; Other Names: Oncaspar; Drug: Methotrexate; 3000m g/m2 civ 6-hour on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.; Drug: Dexamethasone; 40mg ivd on day 1 of each 21 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy Outcome Measure	Study group increase 15% 2-year PFS	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety/Adverse Event Outcome Measure	Number of Participants with Serious and Non-Serious Adverse Events	Up to 36 months

Other Outcome Measures

Outcome Measure	Time Frame
Efficacy Outcome Measure	Up to 36 months

Collaborators and Investigators

• Sponsor: Huiqiang Huang
• Collaborators: Sun Yat-sen University
• Investigators: Study Chair: HuiQiang Huang, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2013
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: March 11, 2014
• First Submitted That Met QC Criteria: March 12, 2014
• First Posted (Estimate): March 13, 2014

Study Record Updates

• Last Update Posted (Actual): March 15, 2021
• Last Update Submitted That Met QC Criteria: March 12, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: thalidomide; Extranodal NK/T-cell lymphoma; PA-Gemox regimen
• 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; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dermatologic Agents; Anti-Bacterial Agents; Leprostatic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Gemcitabine; Dexamethasone; Thalidomide; Oxaliplatin; Methotrexate; Pegaspargase
• Other Study ID Numbers: NKT-SYSUCC-2013