Study Comparing Conventional Dose Combination RVD to High-Dose Treatment With ASCT in the Initial Myeloma up to 65 Years (IFM/DFCI2009)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Celgene Corporation
Janssen-Cilag Ltd.
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT01191060
First received: April 16, 2010
Last updated: May 26, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Multiple Myeloma
Progression Free Survival Prolongation
Disease Progression
Overall Survival
Drug: Lenalidomide, Bortézomib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: up to 4 years ] [ Designated as safety issue: Yes ]
    To compare progression-free survival (PFS) between the Arm A and Arm B.up to 4 years or until progression


Secondary Outcome Measures:
  • Response Rates [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    -Response rates (RR) between the two arms up to 4 years or until progression

  • Time To Progression [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    -Time to progression (TTP) between the two arms up to 4 years or until progression

  • Toxicity comparison [ Time Frame: up to 4 years ] [ Designated as safety issue: Yes ]
    -Toxicity comparison between the two arms randomization up to 4 years or until progression

  • Genetic prognostic groups definition [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    -Genetic prognostic groups definition (evaluated by gene expression profiling-GEP) from randomization up to 4 years or until progression

  • Best treatment examination in each GEP-defined prognostic group. [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
    Best treatment examination in each GEP-defined prognostic group. from randomization up to 4 years or until progression


Enrollment: 700
Study Start Date: October 2010
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B : RVD Treatment with ASCT

RVD q 21 days (2 cycles) Collection of peripheral blood stem cells (PBSCs) using cyclophosphamide and GCSF (type Granocyte® or equivalent)

Autologous stem cell transplant:

Melphalan: infused over two days (day -2 and day -1) or as a single infusion (day-2) according to institutional practice Re-infusion of PBSCs RVD q 21 days (2 cycles) Maintenance Lenalidomide q28 days (12 months)

Drug: Lenalidomide, Bortézomib

Lenalidomide/Bortézomib/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

Other Names:
  • Lenalidomide (REVLIMID®)
  • Bortézomib (VELCADE®)
Experimental: A : RVD treatment without ASCT
RVD q 21 days (2 cycles) Collection of peripheral blood stem cells (PBSCs) using cyclophosphamide and GCSF (type Granocyte® or equivalent) RVD q 21 days (5 cycles) Maintenance Lenalidomide q28 days (12 months)
Drug: Lenalidomide, Bortézomib

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

Other Names:
  • Lenalidomide (REVLIMID®)
  • Bortézomib (VELCADE®)

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01191060

  Hide Study Locations
Locations
France
CH du Pays D'Aix
Aix-en-provence, France, 13 616
CHRU - Hôpital Sud Amiens
AMIENS cedex 1, France, 80054
CHU d'Angers
ANGERS cedex 01, France, 49033
Centre Hospitalier Argenteuil Victor Dupouy
Argenteuil, France, 95 100
Centre Hospitalier H.Duffaut
Avignon, France, 84902
Centre Hospitalier de la côte basque
Bayonne, France, 64109
Hôpital Jean Minjoz
Besançon, France, 25030
Centre Hospitalier de Blois
Blois, France, 41016
Hôpital Avicenne
Bobigny, France, 93009
Polyclinique Bordeaux Nord Aquitaine
Bordeaux, France, 33 300
Hôpital A.Morvan
Brest, France, 29609
CHU Caen Côte de Nacre
Caen, France, 14033
Centre François Baclesse
Caen, France, 14076
CH René Dubos
Cergy-Pontoise, France, 95303
Centre Hospitalier William Morey
Chalon-sur-saone, France, 71 321
CH Chambéry
Chambéry, France, 73011
Hôpital Antoine Béclère
Clamart cedex, France, 92 141
Hôpital d'instruction des armées Percy
Clamart cedex, France, 92141
Pole Santé République
Clermont - Ferrand, France, 63050
CHU d'Estaing
Clermont-Ferrand, France, 63000
CH Louis Pasteur - Colmar
Colmar, France, 68024
CH Sud Francilien
Corbeil-Essonnes, France, 91106
CHU Henri Mondor
Créteil, France, 94 010
CHRU Dijon
Dijon, France, 21000
Centre Hospitalier Général - Dunkerque
Dunkerque, France, 59 385
Hôpital A.Michallon
Grenoble, France, 38043
Centre hospitalier départemental - La Roche sur Yon cedex
La Roche sur Yon cedex, France, 85025
CH de Chartres - Hôpital Louis Pasteur
Le Coudray, France, 26630
Centre Jean Bernard
Le Mans, France, 72000
Centre hospitalier Le Mans
Le Mans, France, 72037
CHRU - Hôpital Claude Huriez
Lille, France, 59037
CHU de Limoges
Limoges, France, 87042
Centre hospitalier Bodelio
Lorient, France, 56322
Centre Léon Bérard
Lyon, France
CHU - Hôpital Edouard Herriot
Lyon, France, 69437
Institut Paoli Calmettes
Marseille, France, 13273
CH Meaux
Meaux, France, 77104
Hopital E Muller
Mulhouse, France, 68100
Centre Catherine de Sienne
Nantes, France, 44 202
CHRU - Hôtel Dieu
Nantes, France, 44093
Hôpital Archet 1
NICE cedex 3, France, 06202
Hôpital de l'Archet
Nice cedex 3, France, 06202
Groupe Hospitalo-Universitaire Carémeau
Nîmes Cédex 9, France, 30029
Institut Curie
Paris, France, 75005
Hôpital Cochin
Paris, France, 75014
Hôpital Saint-Louis
PARIS cedex 10, France, 75475
Hôpital St-Antoine
Paris cedex 12, France, 75571
CH Saint Jean
Perpignan, France, 66046
CHRU - Hôpital du Haut Lévêque
Pessac, France, 33604
Centre Hospitalier Lyon sud
Pierre - Bénite cedex, France, 69495
CHRU - Hôpital Jean Bernard
Poitiers, France, 86021
Centre Hospitalier de la région d'Annecy
Pringy, France, 74374
Hôpital R.Debré
Reims, France, 51092
CHRU - Hôpital de Pontchaillou
Rennes, France, 35033
CHRU - Hôpital Sud
Rennes, France, 35056
Centre Henri Becquerel
Rouen, France, 76038
Groupe Hospitalier Sud Réunion
SAINT-PIERRE cedex, France, 97448
Centre René Huguenin
St Cloud, France, 92210
Centre Hospitalier Yves le Foll
St-Brieuc cedex 1, France, 22 027
Centre Hospitalier Départemental - La réunion St Denis
St-denis, France, 97 405
Institut de Cancérologie de la Loire
St-priest-en-jarez, France, 42 271
Hôpitaux Universitaires de Strasbourg
Strasbourg, France, 67091
University Hospital of Toulouse, Purpan
Toulouse, France, 31059 Cedex 9
CHRU - Hôpital Bretonneau
Tours, France, 37044
Centre Hospitalier de Valence
Valence, France, 26953
Hôpitaux de Brabois
Vandoeuvre cedex, France, 54511
CH Bretagne Atlantique Vannes et Auray
Vannes cedex, France, 56017
Institut Gustave Roussy
Villejuif cedex, France, 94 805
Sponsors and Collaborators
University Hospital, Toulouse
Dana-Farber Cancer Institute
Celgene Corporation
Janssen-Cilag Ltd.
Investigators
Principal Investigator: MICHEL ATTAL, Pr University Hospital of Toulouse
  More Information

No publications provided by University Hospital, Toulouse

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University Hospital, Toulouse
ClinicalTrials.gov Identifier: NCT01191060     History of Changes
Other Study ID Numbers: 09 110 01
Study First Received: April 16, 2010
Last Updated: May 26, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Disease Progression
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Dexamethasone
Bortezomib
Lenalidomide
Thalidomide
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on August 20, 2014