Clinical trial NCT00283985: Association of L-asparaginase-Methotrexate-Dexamethasone for Nasal and Nasal-type Natural Killer (NK)-T-cell Lymphoma
Official title: Phase II Study of an Association of L-asparaginase-Methotrexate-Dexamethasone for Relapsing and/or Refractory Nasal and Nasal-type NK-T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin
Keywords: NK/T-cell lymphoma
Lymphoma
L-asparaginase
Nasal NK-cell lymphoma
Nasal-type NK-cell Lymphoma
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2006-01-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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)

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of chemotherapy
timeFrame: 3 month, 6 month, 9 month, 12 month, 18 month, 24 month
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Département Maladies du Sang
city: Annecy
country: France
facility: CH Annecy
city: Bordeaux
country: France
facility: Service de Radiothérapie, Polyclinique Bordeaux Nord
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Créteil
country: France
facility: Service d'Hématologie Clinique - Hôpital Henri Mondor
city: Dijon
country: France
facility: Service d'Hématologie Clinique, CHU Dijon
city: Evry
country: France
facility: Service d'Hématologie
city: Grenoble
country: France
facility: CHU Grenoble-Hématologie Clinique
city: Lille
country: France
facility: CHU Lille - Maladies du Sang
city: Limoges
country: France
facility: Service d'Hématologie et de Thérapie Cellulaire - CHU Limoges
city: Lorient
country: France
facility: CH Lorient
city: Lyon
country: France
facility: CHU Lyon - Hématologie Clinique
city: Marseille
country: France
facility: Département d'Oncologie - Institut Paoli Calmettes
city: Montpellier
country: France
facility: CHU Montpellier
city: Paris
country: France
facility: Hématologie Adulte, Hôpital Necker
city: Paris
country: France
facility: Département d'Immuno-Hématologie, Hôpital Saint-Louis
city: Paris
country: France
facility: CH Lariboisière
city: Paris
country: France
facility: Hôpital St Antoine
city: Paris
country: France
facility: Service d'Hématologie Clinique, Groupe Hospitalier Necker
city: Paris
country: France
facility: Service d'Hématologie Clinique, Groupe Hospitalier Pitié-Salpétrière
city: Paris
country: France
facility: Service d'Immunologie Clinique 2, Hôpital Saint Louis
city: Reims
country: France
facility: Service d'Hématologie Clinique, CHU de Reims
city: Rouen
country: France
facility: Centre Henri Becquerel-Rouen
city: Saint-Etienne
country: France
facility: Département Hématologie Clinique
city: Toulouse
country: France
facility: CHU Toulouse
Study officials:
affiliation: University Hospital, Limoges
name: Arnaud JACCARD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jaccard A, Gachard N, Marin B, Rogez S, Audrain M, Suarez F, Tilly H, Morschhauser F, Thieblemont C, Ysebaert L, Devidas A, Petit B, de Leval L, Gaulard P, Feuillard J, Bordessoule D, Hermine O; GELA and GOELAMS Intergroup. Efficacy of L-asparaginase with methotrexate and dexamethasone (AspaMetDex regimen) in patients with refractory or relapsing extranodal NK/T-cell lymphoma, a phase 2 study. Blood. 2011 Feb 10;117(6):1834-9. doi: 10.1182/blood-2010-09-307454. Epub 2010 Dec 1.