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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01191060
Other study ID # 09 110 01
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date October 2010
Est. completion date November 30, 2018

Study information

Verified date April 2019
Source University Hospital, Toulouse
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


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).


Recruitment information / eligibility

Status Completed
Enrollment 700
Est. completion date November 30, 2018
Est. primary completion date November 30, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Lenalidomide, Bortezomib
Lenalidomide/Bortézomib/Dexamethasone cycles: Number of cycles: 8 cycles for arm A Cycle length Dosage: Lenalidomide: 25 mg/day on days 1-14 of each cycle Bortézomib: 1.3 mg/m2 on days 1, 4, 8, and 11 for 1 cycle of each cycle Maintenance phase (12 months): Cycle length: 28 days Dosage: Lenalidomide: 10 mg/day continuously for 28 days during 3 months and if the participant tolerates 10 mg/day without complication, a dose increase to 15 mg/day will be allowed
Lenalidomide, Bortezomib
Lenalidomide Bortezomib Dexamethasone cycles: Number of cycles: 5 cycles for arm B Cycle length Dosage: Lenalidomide: 25 mg/day on days 1-14 of each cycle Bortézomib: 1.3 mg/m2 on days 1, 4, 8, and 11 for 1 cycle of each cycle Maintenance phase (12 months): Cycle length: 28 days Dosage: Lenalidomide: 10 mg/day continuously for 28 days during 3 months and if the participant tolerates 10 mg/day without complication, a dose increase to 15 mg/day will be allowed

Locations

Country Name City State
France CH du Pays D'Aix Aix-en-provence
France CHRU - Hôpital Sud Amiens AMIENS cedex 1
France CHU d'Angers ANGERS cedex 01
France Centre Hospitalier Argenteuil Victor Dupouy Argenteuil
France Centre Hospitalier H.Duffaut Avignon
France Centre Hospitalier de la côte basque Bayonne
France Hôpital Jean Minjoz Besançon
France Centre Hospitalier de Blois Blois
France Hôpital Avicenne Bobigny
France Polyclinique Bordeaux Nord Aquitaine Bordeaux
France Hôpital A.Morvan Brest
France Centre François Baclesse Caen
France CHU Caen Côte de Nacre Caen
France CH René Dubos Cergy-Pontoise
France Centre Hospitalier William Morey Chalon-sur-saone
France CH Chambéry Chambéry
France Hôpital Antoine Béclère Clamart cedex
France Hôpital d'instruction des armées Percy Clamart cedex
France Pole Santé République Clermont - Ferrand
France CHU d'Estaing Clermont-Ferrand
France CH Louis Pasteur - Colmar Colmar
France CH Sud Francilien Corbeil-Essonnes
France CHU Henri Mondor Créteil
France CHRU Dijon Dijon
France Centre Hospitalier Général - Dunkerque Dunkerque
France Hôpital A.Michallon Grenoble
France Centre hospitalier départemental - La Roche sur Yon cedex La Roche sur Yon cedex
France CH de Chartres - Hôpital Louis Pasteur Le Coudray
France Centre hospitalier Le Mans Le Mans
France Centre Jean Bernard Le Mans
France CHRU - Hôpital Claude Huriez Lille
France CHU de Limoges Limoges
France Centre hospitalier Bodelio Lorient
France Centre Léon Bérard Lyon
France CHU - Hôpital Edouard Herriot Lyon
France Institut Paoli Calmettes Marseille
France CH Meaux Meaux
France Hopital E Muller Mulhouse
France Hôpitaux de Brabois Nancy
France Centre Catherine de Sienne Nantes
France CHRU - Hôtel Dieu Nantes
France Hôpital Archet 1 NICE cedex 3
France Hôpital de l'Archet Nice cedex 3
France Groupe Hospitalo-Universitaire Carémeau Nîmes Cédex 9
France Hôpital Cochin Paris
France Institut Curie Paris
France Hôpital Saint-Louis PARIS cedex 10
France Hôpital St-Antoine Paris cedex 12
France CH Saint Jean Perpignan
France CHRU - Hôpital du Haut Lévêque Pessac
France Centre Hospitalier Lyon sud Pierre - Bénite cedex
France CHRU - Hôpital Jean Bernard Poitiers
France Centre Hospitalier de la région d'Annecy Pringy
France Hôpital R.Debré Reims
France CHRU - Hôpital de Pontchaillou Rennes
France CHRU - Hôpital Sud Rennes
France Centre Henri Becquerel Rouen
France Groupe Hospitalier Sud Réunion SAINT-PIERRE cedex
France Centre René Huguenin St Cloud
France Centre Hospitalier Yves le Foll St-Brieuc cedex 1
France Centre Hospitalier Départemental - La réunion St Denis St-denis
France Institut de Cancérologie de la Loire St-priest-en-jarez
France Hôpitaux Universitaires de Strasbourg Strasbourg
France University Hospital of Toulouse, Purpan Toulouse
France CHRU - Hôpital Bretonneau Tours
France Centre Hospitalier de Valence Valence
France CH Bretagne Atlantique Vannes et Auray Vannes cedex
France Institut Gustave Roussy Villejuif cedex

Sponsors (4)

Lead Sponsor Collaborator
University Hospital, Toulouse Celgene Corporation, Dana-Farber Cancer Institute, Janssen-Cilag Ltd.

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression Free Survival To compare progression-free survival (PFS) between the Arm A and Arm B up to 4 years or until progression up to 4 years
Secondary Response Rates -Response rates (RR) between the two arms up to 4 years or until progression up to 4 years
Secondary Time To Progression Time to progression (TTP) between the two arms up to 4 years or until progression up to 4 years
Secondary Toxicity comparison Toxicity comparison between the two arms randomization up to 4 years or until progression up to 4 years
Secondary Genetic prognostic groups definition Genetic prognostic groups definition (evaluated by gene expression profiling-GEP) from randomization up to 4 years or until progression up to 4 years
Secondary Best treatment examination in each GEP-defined prognostic group. Best treatment examination in each GEP-defined prognostic group. from randomization up to 4 years or until progression up to 4 years
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