Clinical trial NCT01191060: Study Comparing Conventional Dose Combination RVD to High-Dose Treatment With ASCT in the Initial Myeloma up to 65 Years
Official title: Randomized Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib and Dexamethasone to High-Dose Treatment With ASCT in the Initial Management of Myeloma in Patients up to 65 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myeloma
Keywords: Progression free survival prolongation
Disease Progression
Overall survival
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
name: Celgene Corporation
name: Janssen-Cilag Ltd.
First posted: 2010-08-30
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objective of this study is to determine if, in the era of novel drugs, high dose therapy (HDT) is still necessary in the initial management of multiple myeloma in younger patients. HDT as compared to conventional dose treatment would be considered superior if it significantly prolongs Progression-free survival (by at least 9 months).

Detailed description: Study design Phase III, multicenter, randomized, open-label study designed to evaluate the clinical benefit from the drug combination RVD without immediate high-dose therapy (HDT) followed by lenalidomide maintenance (Arm A) versus RVD plus HDT and PBSCT followed by lenalidomide maintenance (Arm B).

Eligibility criteria: Inclusion Criteria for registration :

(with labs performed within 21 days of initiation of protocol therapy):

* Patients diagnosed with multiple myeloma based on International Myeloma Foundation 2003 Diagnostic Criteria.
* Patients must have symptomatic myeloma with myeloma-related organ damage.
* Patients must have myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains.
* Age between 18 and 65 years at the time of signing the informed consent document.
* ECOG performance status \<2 (Karnofsky ≥ 60%)
* Negative HIV blood test

Exclusion Criteria for registration (section 4.2):

* Participants must not have been treated with any prior systemic therapy for multiple myeloma. Treatment by localized radiotherapy is not an exclusion criterion if an interval of at least two weeks between the end of radiotherapy and initiation of protocol therapy entry in the study is observed. Similarly, the dose of corticosteroids received by the participant should not exceed the equivalent of 160 mg of dexamethasone over a two-week period before initiation of protocol therapy.
* Primary amyloidosis (AL) or myeloma complicated by amylosis.
* Participants may not be receiving any other study investigational agents.
* Participants with known brain metastases
* Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic composition to study agents
* Platelet count \< 50,000/mm3 per µLwithin 21 days of initiation of protocol therapy. Transfusion within 7 days of screening is not allowed to meet platelet eligibility criteria.
* ANC \< 1,000 cells/mm3 within 21 days of initiation of protocol therapy. Growth factor within 7 days of screening is not allowed to meet ANC eligibility criteria.
* Hemoglobin \< 8.0 g/dL within 21 days of initiation of protocol therapy. Transfusion may be used to meet hemoglobin eligibility criteria.
* Hepatic impairment, defined a bilirubin \> 1.5 x institutional upper limit of normal (ULN) \> 2 mg/dL (Patients with benign hyperbilirubinemia (e.g., Gilbert's syndrome) are eligible) and or AST (SGOT), or ALT (SGPT), or alkaline phosphatase \> 2 x ULN
* Renal insufficiency, defined as serum creatinine \> 2.5 mg/dl and/or creatinine clearance \< \<40 60 ml/min (actual or calculated). The Cockgroft-Gault formula should be used for calculating creatinine clearance values, and may be located in Section 4.2
* Respiratory compromise, defined as ventilation tests and with DLCO \< 50%
* Participant must not demonstrate with clinical signs of heart or coronary failure, or evidence of LVEF \< 40%. Participant must not have with myocardial infarction within 6 months prior to enrollment or have New York Heart Association (NYHA Appendix VII) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
* Intercurrent illness including, but not limited to ongoing or active severe infection, known (active or not) infection with hepatitis B or C virus, poorly controlled diabetes, severe uncontrolled psychiatric disorder or psychiatric illness/social situations that would limit compliance with study requirements.
* Participant with previous history of another malignant condition, except for basal cell carcinoma and stage I cervical cancer
* Female participant who is pregnant or breast-feeding
* Inability to comply with an anti-thrombotic treatment regimen
* Peripheral neuropathy ≥ Grade 2 peripheral neuropathy on clinical examination within 21 days of initiation of protocol therapy
* Mental illness likely to interfere with participation in the study and Adults under juridical protection

Primary outcomes:
measure: Progression Free Survival
timeFrame: up to 4 years
Secondary outcomes:
measure: Response Rates
timeFrame: up to 4 years
measure: Time To Progression
timeFrame: up to 4 years
measure: Toxicity comparison
timeFrame: up to 4 years
measure: Genetic prognostic groups definition
timeFrame: up to 4 years
measure: Best treatment examination in each GEP-defined prognostic group.
timeFrame: up to 4 years
Other outcomes:
Locations:
city: Aix-en-provence
country: France
facility: CH du Pays D'Aix
city: AMIENS cedex 1
country: France
facility: CHRU - Hôpital Sud Amiens
city: ANGERS cedex 01
country: France
facility: CHU d'Angers
city: Argenteuil
country: France
facility: Centre Hospitalier Argenteuil Victor Dupouy
city: Avignon
country: France
facility: Centre Hospitalier H.Duffaut
city: Bayonne
country: France
facility: Centre Hospitalier de la côte basque
city: Besançon
country: France
facility: Hôpital Jean Minjoz
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bobigny
country: France
facility: Hôpital Avicenne
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Brest
country: France
facility: Hôpital A.Morvan
city: Caen
country: France
facility: CHU Caen Côte de Nacre
city: Caen
country: France
facility: Centre François Baclesse
city: Cergy-Pontoise
country: France
facility: CH René Dubos
city: Chalon-sur-saone
country: France
facility: Centre Hospitalier William Morey
city: Chambéry
country: France
facility: CH Chambéry
city: Clamart cedex
country: France
facility: Hôpital Antoine Béclère
city: Clamart cedex
country: France
facility: Hôpital d'instruction des armées Percy
city: Clermont - Ferrand
country: France
facility: Pole Santé République
city: Clermont-Ferrand
country: France
facility: CHU d'Estaing
city: Colmar
country: France
facility: CH Louis Pasteur - Colmar
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien
city: Créteil
country: France
facility: CHU Henri Mondor
city: Dijon
country: France
facility: CHRU Dijon
city: Dunkerque
country: France
facility: Centre Hospitalier Général - Dunkerque
city: Grenoble
country: France
facility: Hôpital A.Michallon
city: La Roche sur Yon cedex
country: France
facility: Centre hospitalier départemental - La Roche sur Yon cedex
city: Le Coudray
country: France
facility: CH de Chartres - Hôpital Louis Pasteur
city: Le Mans
country: France
facility: Centre Jean Bernard
city: Le Mans
country: France
facility: Centre hospitalier Le Mans
city: Lille
country: France
facility: CHRU - Hôpital Claude Huriez
city: Limoges
country: France
facility: CHU de Limoges
city: Lorient
country: France
facility: Centre hospitalier Bodelio
city: Lyon
country: France
facility: CHU - Hôpital Edouard Herriot
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Meaux
country: France
facility: CH Meaux
city: Mulhouse
country: France
facility: Hopital E Muller
city: Nancy
country: France
facility: Hôpitaux de Brabois
city: Nantes
country: France
facility: Centre Catherine de Sienne
city: Nantes
country: France
facility: CHRU - Hôtel Dieu
city: NICE cedex 3
country: France
facility: Hôpital Archet 1
city: Nice cedex 3
country: France
facility: Hôpital de l'Archet
city: Nîmes Cédex 9
country: France
facility: Groupe Hospitalo-Universitaire Carémeau
city: PARIS cedex 10
country: France
facility: Hôpital Saint-Louis
city: Paris cedex 12
country: France
facility: Hôpital St-Antoine
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hôpital Cochin
city: Perpignan
country: France
facility: CH Saint Jean
city: Pessac
country: France
facility: CHRU - Hôpital du Haut Lévêque
city: Pierre - Bénite cedex
country: France
facility: Centre Hospitalier Lyon sud
city: Poitiers
country: France
facility: CHRU - Hôpital Jean Bernard
city: Pringy
country: France
facility: Centre Hospitalier de la région d'Annecy
city: Reims
country: France
facility: Hôpital R.Debré
city: Rennes
country: France
facility: CHRU - Hôpital de Pontchaillou
city: Rennes
country: France
facility: CHRU - Hôpital Sud
city: Rouen
country: France
facility: Centre Henri Becquerel
city: SAINT-PIERRE cedex
country: France
facility: Groupe Hospitalier Sud Réunion
city: St Cloud
country: France
facility: Centre René Huguenin
city: St-Brieuc cedex 1
country: France
facility: Centre Hospitalier Yves le Foll
city: St-denis
country: France
facility: Centre Hospitalier Départemental - La réunion St Denis
city: St-priest-en-jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: University Hospital of Toulouse, Purpan
city: Tours
country: France
facility: CHRU - Hôpital Bretonneau
city: Valence
country: France
facility: Centre Hospitalier de Valence
city: Vannes cedex
country: France
facility: CH Bretagne Atlantique Vannes et Auray
city: Villejuif cedex
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: University Hospital of Toulouse
name: MICHEL ATTAL, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Langerhorst P, Noori S, Zajec M, De Rijke YB, Gloerich J, van Gool AJ, Caillon H, Joosten I, Luider TM, Corre J, VanDuijn MM, Dejoie T, Jacobs JFM. Multiple Myeloma Minimal Residual Disease Detection: Targeted Mass Spectrometry in Blood vs Next-Generation Sequencing in Bone Marrow. Clin Chem. 2021 Nov 26;67(12):1689-1698. doi: 10.1093/clinchem/hvab187.
citation: Samur MK, Aktas Samur A, Fulciniti M, Szalat R, Han T, Shammas M, Richardson P, Magrangeas F, Minvielle S, Corre J, Moreau P, Thakurta A, Anderson KC, Parmigiani G, Avet-Loiseau H, Munshi NC. Genome-Wide Somatic Alterations in Multiple Myeloma Reveal a Superior Outcome Group. J Clin Oncol. 2020 Sep 20;38(27):3107-3118. doi: 10.1200/JCO.20.00461. Epub 2020 Jul 20.
citation: Roussel M, Hebraud B, Hulin C, Perrot A, Caillot D, Stoppa AM, Macro M, Escoffre M, Arnulf B, Belhadj K, Karlin L, Garderet L, Facon T, Guo S, Weng J, Dhanasiri S, Leleu X, Moreau P, Attal M. Health-related quality of life results from the IFM 2009 trial: treatment with lenalidomide, bortezomib, and dexamethasone in transplant-eligible patients with newly diagnosed multiple myeloma. Leuk Lymphoma. 2020 Jun;61(6):1323-1333. doi: 10.1080/10428194.2020.1719091. Epub 2020 Feb 22.
citation: Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. doi: 10.1056/NEJMoa1611750.
citation: Dunavin NC, Wei L, Elder P, Phillips GS, Benson DM Jr, Hofmeister CC, Penza S, Greenfield C, Rose KS, Rieser G, Merritt L, Ketcham J, Heerema N, Byrd JC, Devine SM, Efebera YA. Early versus delayed autologous stem cell transplant in patients receiving novel therapies for multiple myeloma. Leuk Lymphoma. 2013 Aug;54(8):1658-64. doi: 10.3109/10428194.2012.751528. Epub 2012 Dec 31.