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

February 27, 2013 updated by: University Hospital, Limoges

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

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.

Study Overview

Status

Completed

Conditions

Lymphoma, Non-Hodgkin

Intervention / Treatment

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)

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

France
- - Angers, France, 49000
    - Département Maladies du Sang
  - Annecy, France
    - CH Annecy
  - Bordeaux, France
    - CHU Bordeaux
  - Bordeaux, France, 33000
    - Service de Radiothérapie, Polyclinique Bordeaux Nord
  - Créteil, France
    - Service d'Hématologie Clinique - Hôpital Henri Mondor
  - Dijon, France
    - Service d'Hématologie Clinique, CHU Dijon
  - Evry, France, 91080
    - Service d'Hematologie
  - Grenoble, France
    - CHU Grenoble-Hématologie Clinique
  - Lille, France
    - CHU Lille - Maladies du Sang
  - Limoges, France
    - Service d'Hématologie et de Thérapie Cellulaire - CHU Limoges
  - Lorient, France
    - CH Lorient
  - Lyon, France
    - CHU Lyon - Hématologie Clinique
  - Marseille, France
    - Département d'Oncologie - Institut Paoli Calmettes
  - Montpellier, France
    - CHU Montpellier
  - Paris, France
    - CH Lariboisière
  - Paris, France
    - Service d'Hématologie Clinique, Groupe Hospitalier Pitié-Salpétrière
  - Paris, France
    - Hôpital St Antoine
  - Paris, France, 75000
    - Hématologie Adulte, Hôpital Necker
  - Paris, France, 75010
    - Département d'Immuno-Hématologie, Hôpital Saint-Louis
  - Paris, France
    - Service d'Hématologie Clinique, Groupe Hospitalier Necker
  - Paris, France
    - Service d'Immunologie Clinique 2, Hôpital Saint Louis
  - Reims, France
    - Service d'Hématologie Clinique, CHU de Reims
  - Rouen, France
    - Centre Henri Becquerel-Rouen
  - Saint-Etienne, France, 42000
    - Département Hématologie Clinique
  - Toulouse, France
    - Chu Toulouse

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: NON_RANDOMIZED
Interventional Model: SINGLE_GROUP
Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy of chemotherapy Time Frame: 3 month, 6 month, 9 month, 12 month, 18 month, 24 month	3 month, 6 month, 9 month, 12 month, 18 month, 24 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Limoges

Investigators

Principal Investigator: Arnaud JACCARD, MD, University Hospital, Limoges

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2006

Primary Completion (ACTUAL)

June 1, 2012

Study Completion (ACTUAL)

June 1, 2012

Study Registration Dates

First Submitted

January 30, 2006

First Submitted That Met QC Criteria