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

Lymphoma, Non-Hodgkin Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00283985
• Other study ID #: I05009
• Status: Completed
• Phase: Phase 2
• First received: January 30, 2006
• Last updated: February 27, 2013
• Start date: February 2006
• Est. completion date: June 2012

Study information

• Verified date: February 2013
• Source: University Hospital, Limoges
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell

Intervention

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

Locations

Country	Name	City	State
France	Département Maladies du Sang	Angers
France	CH Annecy	Annecy
France	CHU Bordeaux	Bordeaux
France	Service de Radiothérapie, Polyclinique Bordeaux Nord	Bordeaux
France	Service d'Hématologie Clinique - Hôpital Henri Mondor	Créteil
France	Service d'Hématologie Clinique, CHU Dijon	Dijon
France	Service d'Hématologie	Evry
France	CHU Grenoble-Hématologie Clinique	Grenoble
France	CHU Lille - Maladies du Sang	Lille
France	Service d'Hématologie et de Thérapie Cellulaire - CHU Limoges	Limoges
France	CH Lorient	Lorient
France	CHU Lyon - Hématologie Clinique	Lyon
France	Département d'Oncologie - Institut Paoli Calmettes	Marseille
France	CHU Montpellier	Montpellier
France	CH Lariboisière	Paris
France	Département d'Immuno-Hématologie, Hôpital Saint-Louis	Paris
France	Hématologie Adulte, Hôpital Necker	Paris
France	Hôpital St Antoine	Paris
France	Service d'Hématologie Clinique, Groupe Hospitalier Necker	Paris
France	Service d'Hématologie Clinique, Groupe Hospitalier Pitié-Salpétrière	Paris
France	Service d'Immunologie Clinique 2, Hôpital Saint Louis	Paris
France	Service d'Hématologie Clinique, CHU de Reims	Reims
France	Centre Henri Becquerel-Rouen	Rouen
France	Département Hématologie Clinique	Saint-Etienne
France	CHU Toulouse	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy of chemotherapy		3 month, 6 month, 9 month, 12 month, 18 month, 24 month	Yes