Clinical trial NCT03603847: Prospective Study of the Prognostic Value of New Markers in Adults With ALK-positive Large Anaplastic Lymphoma
Official title: Prospective Study of the Prognostic Value of New Markers in Adults With ALK-positive Large Anaplastic Lymphoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Anaplastic Large Cell Lymphoma, ALK-Positive
Lead sponsor: The Lymphoma Academic Research Organisation
Sponsor class: OTHER
Collaborators: name: Hôpital Necker-Enfants Malades
name: Fondation ARC
name: Pfizer
name: Takeda
First posted: 2018-07-27
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult Anaplastic large-cell lymphoma ALK+

Brief summary: The study aims to evaluate the prognostic value on the complete metabolic response rate (MCR), the incidence of relapse / progression, the Progression Free Survival (PFS) and the Overall Survival (OS).

* at diagnosis
* after the first cycle of CHOEP (early evaluation)
* at the end of treatment

Detailed description: ALK-positive anaplastic large cell (anaplastic large-cell lymphoma, ALCL) is a rare adult disease for which almost all published studies are retrospective. The overall survival (OS) at 5 years varies from 70 to 87%. A recent international pooled analysis showed that the International Prognostic Index (IPI) had good predictive value for the PFS and the OS.

In children, new prognostic factors have been identified: the titre of circulating anti-ALK antibodies (inverse correlation between the antibody titre and the prognosis), the detection of a NPM-ALK transcript in the blood at diagnosis (minimal disseminated disease, MDD); correlation between MDD positivity and pejorative prognosis) and its minimal residual disease (MRD), and the histological subtype (common versus small cells / lymphohistiocytic).

The predictive value of the oncogenic profile of ALK-positive ALCL and circulating tumor DNA will be studied in this study.

* At diagnosis (before starting treatment):
* Cycle 2 Day 1 (before starting cycle 2 treatment):
* At the end of treatment evaluation:

  40 patients treated with 6 cycles of CHOEP every 3 weeks and 1 lumbar puncture at diagnosis with intrathecal prophylaxis with methotrexate will be included prospectively.

During a 2-year period, relapses / progressions and patient deaths will be monitored for the calculation of the incidence of relapse / progression, progression free survival (PFS) and overall survival (OS).

Eligibility criteria: Inclusion Criteria:

Over 18 years old Diagnosed with Anaplastic large-cell lymphoma ALK+

Planned treatment : 6 cycles of CHOEP 21

Planned lumbar puncture at diagnosis or at the first cycle with intrathecal prophylaxis with methotrexate (15 mg) at the first cycle

Planned interim positron emission tomograph (PET)-scan after 3 cycles of treatment and at the end of treatment according to the center standard of care

Exclusion Criteria:

Involvement of the central nervous system

Intent of Autologous stem-cell transplant in first line

Primary outcomes:
measure: Prognostic value of biological parameters on the complete metabolic response rate (MCR)
timeFrame: Day 0
Secondary outcomes:
measure: Prognostic value of biological parameters on the complete metabolic response rate (MCR)
timeFrame: 1 month
measure: Prognostic value of biological parameters on the complete metabolic response rate (MCR)
timeFrame: 2 years
measure: Prognostic value of biological parameters on the incidence of relapse
timeFrame: Day 0
measure: Prognostic value of biological parameters on the incidence of relapse
timeFrame: 1 month
measure: Prognostic value of biological parameters on the incidence relapse
timeFrame: 2 years
measure: Prognostic value of biological parameters on the Progression Free Survival (PFS)
timeFrame: Day 0
measure: Prognostic value of biological parameters on the Progression Free Survival (PFS)
timeFrame: 1 month
measure: Prognostic value of biological parameters on the Progression Free Survival (PFS)
timeFrame: 2 years
measure: Prognostic value of biological parameters on the Overall Survival (OS)
timeFrame: Day 0
measure: Prognostic value of biological parameters on the Overall Survival (OS)
timeFrame: 1 month
measure: Prognostic value of biological parameters on the Overall Survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens - Hôpital Sud
city: Clermont-Ferrand
country: France
facility: CHU d'Estaing
city: Creteil
country: France
facility: APHP - Hopital Henri Mondor
city: Grenoble
country: France
facility: CHU Grenoble
city: Lille
country: France
facility: CHRU de Lille - Hôpital Claude Huriez
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Paris Cedex 10
country: France
facility: APHP - Hôpital Saint Louis
city: Paris
country: France
facility: APHP - Hôpital Necker
city: Pessac
country: France
facility: CHU Bordeaux - Centre François Magendie
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Rennes
country: France
facility: CHU de Rennes - Hôpital de Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Strasbourg
country: France
facility: CHRU de Strasbourg
city: Toulouse
country: France
facility: Institut Universitaire du Cancer de Toulouse - Oncopole
city: Vandoeuvre les Nancy
country: France
facility: CHU Brabois
Study officials:
affiliation: Hôpital Necker-Enfants Malades
name: David SIBON, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sibon D, Fournier M, Briere J, Lamant L, Haioun C, Coiffier B, Bologna S, Morel P, Gabarre J, Hermine O, Sonet A, Gisselbrecht C, Delsol G, Gaulard P, Tilly H. Long-term outcome of adults with systemic anaplastic large-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte trials. J Clin Oncol. 2012 Nov 10;30(32):3939-46. doi: 10.1200/JCO.2012.42.2345. Epub 2012 Oct 8.
citation: Damm-Welk C, Mussolin L, Zimmermann M, Pillon M, Klapper W, Oschlies I, d'Amore ES, Reiter A, Woessmann W, Rosolen A. Early assessment of minimal residual disease identifies patients at very high relapse risk in NPM-ALK-positive anaplastic large-cell lymphoma. Blood. 2014 Jan 16;123(3):334-7. doi: 10.1182/blood-2013-09-526202. Epub 2013 Dec 2.
citation: Damm-Welk C, Pillon M, Woessmann W, Mussolin L. Prognostic factors in paediatric anaplastic large cell lymphoma: role of ALK. Front Biosci (Schol Ed). 2015 Jun 1;7(2):205-16. doi: 10.2741/S434.
citation: Lamant L, McCarthy K, d'Amore E, Klapper W, Nakagawa A, Fraga M, Maldyk J, Simonitsch-Klupp I, Oschlies I, Delsol G, Mauguen A, Brugieres L, Le Deley MC. Prognostic impact of morphologic and phenotypic features of childhood ALK-positive anaplastic large-cell lymphoma: results of the ALCL99 study. J Clin Oncol. 2011 Dec 10;29(35):4669-76. doi: 10.1200/JCO.2011.36.5411. Epub 2011 Nov 14.