Association of L-asparaginase-Methotrexate-Dexamethasone for Nasal and Nasal-type Natural Killer (NK)-T-cell Lymphoma

Study Overview
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Brief Summary
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Nasal/nasal type NK-T-cell lymphoma is a rare and severe type of non-Hodgkin's lymphoma (NHL) more frequent in Asia than in western countries. When localised, radiotherapy seems to be the best treatment. When radiotherapy cannot be used because of dissemination or relapse, chemotherapy protocols used for other types of NHL give poor results and survival is poor. Recently papers from China and Japan reported the efficacy of a drug: l-asparaginase, usually used to treat acute lymphoblastic leukemia. In vitro a selective apoptosis of NK-cell tumours by l-asparaginase was shown on tumour cell lines and samples. The investigators propose a phase II protocol for patients with refractory or relapsing nasal/nasal type NK-T-cell lymphoma using a regimen combining l-asparaginase, methotrexate and dexamethasone. Biological studies will be conducted trying to find factors which could predict responses to this chemotherapy. Since january 2009, the study concerns all patients with nasal/nasal type NK-T-cell lymphoma who have not received asparaginase before.

Detailed Description
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Primary Objective: Determine the overall and complete response rate Secondary Objectives: To evaluate survival without progression To evaluate total survival. To evaluate the tolerance and the side effects of the treatment. To evaluate the duration and the mode of hospitalization of the patients treated by this therapeutic association. To constitute a bank of biological samples - serum, tumoral, ADN, ARN to allow prognostic studies implying virus EBV, p53, CD94, C-kit and asparagine synthetase gene in order to better understand the mechanisms of the cancerogenesis of this variety of cytotoxic LNH and to identify the predictive factors of response to the asparaginase. Sampling: For each patient included in the protocol, the following sampling will be carried out with the diagnosis: Biopsy, Medullary biopsy Medullary aspiration blood: 3 tubes of 7 ml on EDTA and 3 tubs of 7 ml with heparin Treatment: All the patients included will receive three cures separated by 3 weeks (J1, J22, J43): J1: Methotrexate 3 gr/m2 J2, J4, J6 and J8: Kidrolase® 6000 u/m2 J1 with J4: Dexamethasone 40 mg (20 mg if age > 70 years)

Official Title
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Phase II Study of an Association of L-asparaginase-Methotrexate-Dexamethasone for Relapsing and/or Refractory Nasal and Nasal-type NK-T-cell Lymphoma

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: Kidrolase
* Drug: Methotrexate
* Drug: Dexamethasone
* Drug: Erwinase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with relapsing/refractory T-NK/NK lymphoma: Ages 18 years and above Patients must have a diagnosis of NK-cell (or T-NK) non-Hodgkin's lymphoma, nasal or nasal-type. Stage I, II, III, or IV disease Creatinine less than 3 x upper limit of normal (ULN) Able to give informed consent No prior treatment with asparaginase Patients with T-NK/NK lymphoma (de novo patients ): Ages 18 years and above Patients must have a diagnosis of NK-cell (or T-NK) non-Hodgkin's lymphoma, nasal or nasal-type. Stage I, II, III, or IV disease Creatinine less than 3 x upper limit of normal (ULN) Able to give informed consent no prior chemotherapy or radiotherapy Exclusion Criteria: Patients who are pregnant or nursing Any factor which might limit the patient's ability to provide informed consent Liver insufficiency Evolutive thrombosis

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Kidrolase|6000 u/ m2 IM at J2, J4 and J6 and J8. 3 to 6 cycles.|
|Drug: Methotrexate|3 gr/m2 at J1|
|Drug: Dexamethasone|40 mg/ per os at J1, J2 and J4.|
|Drug: Erwinase|In case of allergy to Kidrolase 20000 u/m2 en IM at J2, J4, J6 et J8. 3 to 6 cycles|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of chemotherapy |  | 3 month, 6 month, 9 month, 12 month, 18 month, 24 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NK/T-cell lymphoma, Lymphoma, L-asparaginase, Nasal NK-cell lymphoma, Nasal-type NK-cell Lymphoma