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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Limoges
ClinicalTrials.gov Identifier:
NCT00283985
First received: January 30, 2006
Last updated: February 27, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Lymphoma, Non-Hodgkin
Drug: Kidrolase
Drug: Methotrexate
Drug: Dexamethasone
Drug: Erwinase
Phase 2

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

Resource links provided by NLM:


Further study details as provided by University Hospital, Limoges:

Primary Outcome Measures:
  • Efficacy of chemotherapy [ Time Frame: 3 month, 6 month, 9 month, 12 month, 18 month, 24 month ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: February 2006
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00283985

Locations
France
Département Maladies du Sang
Angers, France, 49000
CH Annecy
Annecy, France
Service de Radiothérapie, Polyclinique Bordeaux Nord
Bordeaux, France, 33000
CHU Bordeaux
Bordeaux, France
Service d'Hématologie Clinique - Hôpital Henri Mondor
Créteil, France
Service d'Hématologie Clinique, CHU Dijon
Dijon, France
Service d'Hématologie
Evry, France, 91080
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
Département d'Immuno-Hématologie, Hôpital Saint-Louis
Paris, France, 75010
Service d'Hématologie Clinique, Groupe Hospitalier Pitié-Salpétrière
Paris, France
Hématologie Adulte, Hôpital Necker
Paris, France, 75000
Service d'Immunologie Clinique 2, Hôpital Saint Louis
Paris, France
Service d'Hématologie Clinique, Groupe Hospitalier Necker
Paris, France
CH Lariboisière
Paris, France
Hôpital St Antoine
Paris, France
Service d'Hématologie Clinique, CHU de Reims
Reims, France
Centre Henri Becquerel-Rouen
Rouen, France
Département Hématologie Clinique
Saint-Etienne, France, 42000
CHU Toulouse
Toulouse, France
Sponsors and Collaborators
University Hospital, Limoges
Investigators
Principal Investigator: Arnaud JACCARD, MD University Hospital, Limoges
  More Information

No publications provided by University Hospital, Limoges

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Limoges
ClinicalTrials.gov Identifier: NCT00283985     History of Changes
Other Study ID Numbers: I05009
Study First Received: January 30, 2006
Last Updated: February 27, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Limoges:
NK/T-cell lymphoma
Lymphoma
L-asparaginase
Nasal NK-cell lymphoma
Nasal-type NK-cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Asparaginase
Dexamethasone
Methotrexate
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Protease Inhibitors

ClinicalTrials.gov processed this record on April 21, 2014