NCT01191060

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
700

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Oct 2010

Longer than P75 for phase_3

Geographic Reach
1 country

68 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 16, 2010

Completed
5 months until next milestone

First Posted

Study publicly available on registry

August 30, 2010

Completed
1 month until next milestone

Study Start

First participant enrolled

October 1, 2010

Completed
8.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2018

Completed
Last Updated

April 18, 2019

Status Verified

April 1, 2019

Enrollment Period

8.2 years

First QC Date

April 16, 2010

Last Update Submit

April 16, 2019

Conditions

Keywords

Progression free survival prolongationDisease ProgressionOverall survival

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (5)

  • Response Rates

    up to 4 years

  • Time To Progression

    up to 4 years

  • Toxicity comparison

    up to 4 years

  • Genetic prognostic groups definition

    up to 4 years

  • Best treatment examination in each GEP-defined prognostic group.

    up to 4 years

Study Arms (2)

lenalidomide, bortezomib with ASCT

EXPERIMENTAL

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, Bortezomib

lenalidomide, bortezomib without ASCT

EXPERIMENTAL

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, Bortezomib

Interventions

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

Also known as: Lenalidomide (REVLIMID®), Bortezomib (VELCADE®)
lenalidomide, bortezomib without ASCT

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • (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

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (68)

CH du Pays D'Aix

Aix-en-Provence, 13 616, France

Location

CHRU - Hôpital Sud Amiens

Amiens, 80054, France

Location

CHU d'Angers

Angers, 49033, France

Location

Centre Hospitalier Argenteuil Victor Dupouy

Argenteuil, 95 100, France

Location

Centre Hospitalier H.Duffaut

Avignon, 84902, France

Location

Centre Hospitalier de la côte basque

Bayonne, 64109, France

Location

Hôpital Jean Minjoz

Besançon, 25030, France

Location

Centre Hospitalier de Blois

Blois, 41016, France

Location

Hôpital Avicenne

Bobigny, 93009, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33 300, France

Location

Hôpital A.Morvan

Brest, 29609, France

Location

CHU Caen Côte de Nacre

Caen, 14033, France

Location

Centre François Baclesse

Caen, 14076, France

Location

CH René Dubos

Cergy-Pontoise, 95303, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, 71 321, France

Location

CH Chambéry

Chambéry, 73011, France

Location

Hôpital Antoine Béclère

Clamart, 92 141, France

Location

Hôpital d'instruction des armées Percy

Clamart, 92141, France

Location

CHU d'Estaing

Clermont-Ferrand, 63000, France

Location

Pole Santé République

Clermont-Ferrand, 63050, France

Location

CH Louis Pasteur - Colmar

Colmar, 68024, France

Location

CH Sud Francilien

Corbeil-Essonnes, 91106, France

Location

CHU Henri Mondor

Créteil, 94 010, France

Location

CHRU Dijon

Dijon, 21000, France

Location

Centre Hospitalier Général - Dunkerque

Dunkirk, 59 385, France

Location

Hôpital A.Michallon

Grenoble, 38043, France

Location

Centre hospitalier départemental - La Roche sur Yon cedex

La Roche-sur-Yon, 85025, France

Location

CH de Chartres - Hôpital Louis Pasteur

Le Coudray, 26630, France

Location

Centre Jean Bernard

Le Mans, 72000, France

Location

Centre hospitalier Le Mans

Le Mans, 72037, France

Location

CHRU - Hôpital Claude Huriez

Lille, 59037, France

Location

CHU de Limoges

Limoges, 87042, France

Location

Centre hospitalier Bodelio

Lorient, 56322, France

Location

CHU - Hôpital Edouard Herriot

Lyon, 69437, France

Location

Centre Léon Bérard

Lyon, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

CH Meaux

Meaux, 77104, France

Location

Hopital E Muller

Mulhouse, 68100, France

Location

Hôpitaux de Brabois

Nancy, 54511, France

Location

Centre Catherine de Sienne

Nantes, 44 202, France

Location

CHRU - Hôtel Dieu

Nantes, 44093, France

Location

Hôpital Archet 1

Nice, 06202, France

Location

Hôpital de l'Archet

Nice, 06202, France

Location

Groupe Hospitalo-Universitaire Carémeau

Nîmes Cédex 9, 30029, France

Location

Institut Curie

Paris, 75005, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

Hôpital St-Antoine

Paris, 75571, France

Location

CH Saint Jean

Perpignan, 66046, France

Location

CHRU - Hôpital du Haut Lévêque

Pessac, 33604, France

Location

Centre Hospitalier Lyon sud

Pierre-Bénite, 69495, France

Location

CHRU - Hôpital Jean Bernard

Poitiers, 86021, France

Location

Centre Hospitalier de la région d'Annecy

Pringy, 74374, France

Location

Hôpital R.Debré

Reims, 51092, France

Location

CHRU - Hôpital de Pontchaillou

Rennes, 35033, France

Location

CHRU - Hôpital Sud

Rennes, 35056, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Centre Hospitalier Yves le Foll

Saint-Brieuc, 22 027, France

Location

Centre René Huguenin

Saint-Cloud, 92210, France

Location

Centre Hospitalier Départemental - La réunion St Denis

Saint-Denis, 97 405, France

Location

Groupe Hospitalier Sud Réunion

Saint-Pierre, 97448, France

Location

Institut de Cancérologie de la Loire

Saint-Priest-en-Jarez, 42 271, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

University Hospital of Toulouse, Purpan

Toulouse, 31059 Cedex 9, France

Location

CHRU - Hôpital Bretonneau

Tours, 37044, France

Location

Centre Hospitalier de Valence

Valence, 26953, France

Location

CH Bretagne Atlantique Vannes et Auray

Vannes, 56017, France

Location

Institut Gustave Roussy

Villejuif, 94 805, France

Location

Related Publications (7)

  • Rosinol L, Hebraud B, Oriol A, Colin AL, Rios Tamayo R, Hulin C, Blanchard MJ, Caillot D, Sureda A, Hernandez MT, Arnulf B, Mateos MV, Macro M, San-Miguel J, Belhadj K, Lahuerta JJ, Garelik MB, Blade J, Moreau P. Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma. Front Oncol. 2023 Nov 2;13:1197340. doi: 10.3389/fonc.2023.1197340. eCollection 2023.

  • Noori S, Wijnands C, Langerhorst P, Bonifay V, Stingl C, Touzeau C, Corre J, Perrot A, Moreau P, Caillon H, Luider TM, Dejoie T, Jacobs JFM, van Duijn MM. Dynamic monitoring of myeloma minimal residual disease with targeted mass spectrometry. Blood Cancer J. 2023 Feb 24;13(1):30. doi: 10.1038/s41408-023-00803-z. No abstract available.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

MeSH Terms

Conditions

Neoplasms, Plasma CellDisease Progression

Interventions

LenalidomideBortezomib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingBoronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsPyrazines

Study Officials

  • MICHEL ATTAL, MD PhD

    University Hospital of Toulouse

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 16, 2010

First Posted

August 30, 2010

Study Start

October 1, 2010

Primary Completion

November 30, 2018

Study Completion

November 30, 2018

Last Updated

April 18, 2019

Record last verified: 2019-04

Locations