Study Comparing Conventional Dose Combination RVD to High-Dose Treatment With ASCT in the Initial Myeloma up to 65 Years

Myeloma Clinical Trial

— IFM/DFCI2009  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01191060
• Other study ID #: 09 110 01
• Status: Completed
• Phase: Phase 3
• 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
• 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Myeloma
• Neoplasms, Plasma Cell

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