CHOP vs GEM-P in 1st Line Treatment of T-cell Lymphoma, Multicentre Phase II Study

Study Overview
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Brief Summary
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This is a randomised, open-label phase II study comparing GEM-P chemotherapy (experimental arm) with CHOP (control arm) in previously untreated T-cell lymphoma. Eligible patients will be randomised 1:1 between 4-weekly GEM-P or 3-weekly CHOP chemotherapy.

Detailed Description
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Background: T-cell lymphoma is an aggressive rare subset of Non-Hodgkin lymphoma (NHL) comprising several different subtypes of disease within this group. No standard first-line treatment exists for T-cell lymphoma as published series are small, with heterogeneous populations and often retrospective. Protocol Synopsis, Study Period: 5 years Objectives: Primary: • To compare the complete response rate of GEM-P with CHOP chemotherapy in the first line treatment of patients with T-Cell Lymphoma. Secondary: To investigate, between both arms: Rate of metabolic complete response Toxicity of treatment Overall survival (OS) Progression Free Survival (PFS) Exploratory: • Investigate impact of International Prognostic Index (IPI) on the outcomes response rate, PFS and OS Study Design: A randomised multi-centre open-label phase II study Indication: Previously untreated T-Cell lymphoma No of Participants: 186 (93 patients in each arm) Main Eligibility Criteria: Histologically proven T-cell lymphoma of the following subtypes: Peripheral T-cell lymphoma NOS Systemic Anaplastic large cell lymphoma (ALCL) Anaplastic lymphoma kinase (ALK) negative cases only Angioimmunoblastic T-cell lymphoma Hepatosplenic gamma/ delta T-cell lymphoma Enteropathy-associated T-cell lymphoma Bulky Stage I, Stage II, III or IV No prior chemotherapy regimen Patients aged 18 years or over. WHO performance status 0,1 or 2 Adequate organ function: No Central Nervous System(CNS) or leptomeningeal involvement with lymphoma No treatment for lymphoma within 4 weeks of commencing trial therapy No known HIV, active Hepatitis B or C infection Treatment: CHOP: cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 days. GEM-P: gemcitabine, methylprednisolone, cisplatin every 28 days. Assessment Schedule: Patients will be reviewed at baseline and prior to each scheduled dose of treatment for toxicity Radiological tumour assessment will be done with CT scan after every 2 cycles in Arm A and after cycle 1, 3 and 4 in Arm B PET/CT scan will be performed at baseline and upon completion of treatment.. Follow up after completion of treatment will be 3, 6, 9, 12, 18, 24 months then annually for 5 years in total. CT scan will be performed at 3 & 12 months. Following disease progression patients will be followed for survival every 3 months until death

Official Title
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CHEMO-T: Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone (CHOP) Versus Gemcitabine, Cisplatin and Methyl Prednisolone (GEM-P) in the First Line Treatment Of T-cell Lymphoma,a Multicentre Randomised Phase II Study

Conditions
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Peripheral T-cell Lymphoma NOS, Anaplastic Large Cell Lymphoma, ALK-Negative, Angioimmunoblastic T-cell Lymphoma, Hepatosplenic Gamma/ Delta T-cell Lymphoma, Enteropathy-Associated T-Cell Lymphoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Gemcitabine
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisolone
* Drug: methylprednisolone
* Drug: Cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated, histologically proven T-cell Lymphoma (any of the following): Peripheral T-cell lymphoma Not Otherwise Specified (PTCL NOS) Systemic Anaplastic large cell lymphoma (ALCL) ALK negative cases only Angioimmunoblastic T-cell lymphoma Hepatosplenic gamma/ delta T-cell lymphoma Enteropathy-associated T-cell lymphoma (EATL) Bulky stage I not being considered for reduced chemotherapy plus involved field radiotherapy or stage II, III or IV. Patient is male or female, and ≥18 years of age on the day of signing informed consent. WHO performance status 0, 1 or 2. Cross sectional imaging from a baseline contrast enhanced CT should show at least one measurable disease site that is at least 2 cm in longest diameter and measurable in two perpendicular dimensions with or without corresponding Fluorodeoxyglucose(FDG) avid lesions. Adequate cardiac function; formal assessment of left ventricular ejection fraction is only required if clinically indicated (a baseline echocardiogram should be done for patients with either hypertension, age > 60 years or history of cardiac disease) Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.0x109/l; white blood cell count ≥ 3x109/l; platelets ≥ 100x109/l; haemoglobin (Hb) ≥ 9g/dl (can be post-transfusion), unless deemed disease related Adequate renal function: calculated creatinine clearance ≥50ml/minute. Adequate liver function: serum bilirubin ≤1.5x Upper limit of normal (ULN); Alanine transaminase/Aspartate transaminase (ALT/AST) ≤2.5x ULN; ALP ≤3x ULN (in the absence of liver metastases). If liver metastases are present, ALT, AST or Alkaline phosphatase (ALP) ≤5x ULN are permitted. Isolated hyperbilirubinaemia due to Gilbert's disease is acceptable Female patient of childbearing potential must have a negative serum or urine β-human chorionic gonadotropin(hCG)pregnancy test at baseline. Written informed consent must be obtained prior to start of study treatments. Scans and bone marrow biopsies performed within 4 weeks of commencement of therapy will be acceptable provided they have been performed according to study requirements. Patient agreeable to use contraception for the period of study treatment and up to 12 months after the last dose of study drugs. Exclusion Criteria: Documented or symptomatic central nervous system involvement or leptomeningeal disease. Patients with no measurable disease on the contrast enhanced CT scan at baseline. Any other clinically significant disease or co-morbidity which may adversely affect the safe delivery of treatment within this trial. Any other malignancies diagnosed or treated within the last 5 years (other than curatively treated basal cell carcinoma of the skin and/or in situ carcinoma of the cervix). Treatment with another investigational agent within 30 days of commencing study treatment. Known positive tests for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or active hepatitis B infection. Patient is pregnant or breastfeeding, or expecting to conceive or father children within one year of finishing study treatment. Patients with poorly controlled diabetes mellitus Hypersensitivity or contraindication to any of the study drugs as stated in the Summaries of product characteristics(SmPCs)for each of the study drugs. Patients with previous cardiac infarct but satisfactory cardiac function may be allowed at the discretion of Chief Investigator.

Ages Eligible for Study
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Minimum Age: 18 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: Chemotherapy GEM-P<br>Gemcitabine, Methylprednisolone, Cisplatin | Drug: Gemcitabine<br>* 1000mg/m2 IV Days 1, 8, 15 every 28 days<br>Drug: methylprednisolone<br>* 1000mg oral or IV Days 1-5 every 28 days<br>Drug: Cisplatin<br>* 100mg/m2 IV Day 15 every 28 days<br>|
| Active Comparator: Chemotherapy CHOP<br>Cyclophosphamide, Doxorubicin, Vincristine, Prednisolone | Drug: Cyclophosphamide<br>* 750mg/m2 IV every 21 days<br>Drug: Doxorubicin<br>* 50mg/m2 IV every 21 days<br>Drug: Vincristine<br>* 1.4mg/m2 (max 2mg) IV every 21 days<br>Drug: Prednisolone<br>* 100mg PO Days 1-5 every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete response rate (CR/CRu) |  | approximately 20 weeks after randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity | using Common Terminology Criteria for Adverse Events (CTCAE)v4.0 | approximately 20 weeks after randomisation | 
| Overall Survival |  | 1 and 2 years | 
| Progression Free survival |  | 1 and 2 years | 
| Metabolic Complete Response Rate |  | approximately 20 weeks after randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T-Cell Lymphoma, Untreated