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

Sponsor

University Hospital, Toulouse (Other)

Overall Status

Completed

CT.gov ID

NCT01191060

Collaborator

Dana-Farber Cancer Institute (Other), Celgene Corporation (Industry), Janssen-Cilag Ltd. (Industry)

700

Enrollment

Locations

Arms

Actual Duration (Months)

10.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Myeloma	Drug: Lenalidomide, Bortezomib Drug: Lenalidomide, Bortezomib	Phase 3

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

700 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Actual Study Start Date :

Oct 1, 2010

Actual Primary Completion Date :

Nov 30, 2018

Actual Study Completion Date :

Nov 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lenalidomide, bortezomib 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, 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 Other Names: Lenalidomide (REVLIMID®) Bortézomib (VELCADE®)
Experimental: lenalidomide, bortezomib 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, 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 Other Names: Lenalidomide (REVLIMID®) Bortezomib (VELCADE®)

Arm

Intervention/Treatment

Experimental: lenalidomide, bortezomib 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, 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

Other Names:

Lenalidomide (REVLIMID®)

Bortézomib (VELCADE®)

Experimental: lenalidomide, bortezomib 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, 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

Other Names:

Lenalidomide (REVLIMID®)

Bortezomib (VELCADE®)

Outcome Measures

Primary Outcome Measures

Progression Free Survival [up to 4 years]
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 [up to 4 years]
-Response rates (RR) between the two arms up to 4 years or until progression
Time To Progression [up to 4 years]
Time to progression (TTP) between the two arms up to 4 years or until progression
Toxicity comparison [up to 4 years]
Toxicity comparison between the two arms randomization up to 4 years or until progression
Genetic prognostic groups definition [up to 4 years]
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. [up to 4 years]
Best treatment examination in each GEP-defined prognostic group. from randomization up to 4 years or until progression

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	Country	Postal Code
1	CH du Pays D'Aix	Aix-en-provence	France	13 616
2	CHRU - Hôpital Sud Amiens	AMIENS cedex 1	France	80054
3	CHU d'Angers	ANGERS cedex 01	France	49033
4	Centre Hospitalier Argenteuil Victor Dupouy	Argenteuil	France	95 100
5	Centre Hospitalier H.Duffaut	Avignon	France	84902
6	Centre Hospitalier de la côte basque	Bayonne	France	64109
7	Hôpital Jean Minjoz	Besançon	France	25030
8	Centre Hospitalier de Blois	Blois	France	41016
9	Hôpital Avicenne	Bobigny	France	93009
10	Polyclinique Bordeaux Nord Aquitaine	Bordeaux	France	33 300
11	Hôpital A.Morvan	Brest	France	29609
12	CHU Caen Côte de Nacre	Caen	France	14033
13	Centre François Baclesse	Caen	France	14076
14	CH René Dubos	Cergy-Pontoise	France	95303
15	Centre Hospitalier William Morey	Chalon-sur-saone	France	71 321
16	CH Chambéry	Chambéry	France	73011
17	Hôpital Antoine Béclère	Clamart cedex	France	92 141
18	Hôpital d'instruction des armées Percy	Clamart cedex	France	92141
19	Pole Santé République	Clermont - Ferrand	France	63050
20	CHU d'Estaing	Clermont-Ferrand	France	63000
21	CH Louis Pasteur - Colmar	Colmar	France	68024
22	CH Sud Francilien	Corbeil-Essonnes	France	91106
23	CHU Henri Mondor	Créteil	France	94 010
24	CHRU Dijon	Dijon	France	21000
25	Centre Hospitalier Général - Dunkerque	Dunkerque	France	59 385
26	Hôpital A.Michallon	Grenoble	France	38043
27	Centre hospitalier départemental - La Roche sur Yon cedex	La Roche sur Yon cedex	France	85025
28	CH de Chartres - Hôpital Louis Pasteur	Le Coudray	France	26630
29	Centre Jean Bernard	Le Mans	France	72000
30	Centre hospitalier Le Mans	Le Mans	France	72037
31	CHRU - Hôpital Claude Huriez	Lille	France	59037
32	CHU de Limoges	Limoges	France	87042
33	Centre hospitalier Bodelio	Lorient	France	56322
34	CHU - Hôpital Edouard Herriot	Lyon	France	69437
35	Centre Léon Bérard	Lyon	France
36	Institut Paoli Calmettes	Marseille	France	13273
37	CH Meaux	Meaux	France	77104
38	Hopital E Muller	Mulhouse	France	68100
39	Hôpitaux de Brabois	Nancy	France	54511
40	Centre Catherine de Sienne	Nantes	France	44 202
41	CHRU - Hôtel Dieu	Nantes	France	44093
42	Hôpital Archet 1	NICE cedex 3	France	06202
43	Hôpital de l'Archet	Nice cedex 3	France	06202
44	Groupe Hospitalo-Universitaire Carémeau	Nîmes Cédex 9	France	30029
45	Hôpital Saint-Louis	PARIS cedex 10	France	75475
46	Hôpital St-Antoine	Paris cedex 12	France	75571
47	Institut Curie	Paris	France	75005
48	Hôpital Cochin	Paris	France	75014
49	CH Saint Jean	Perpignan	France	66046
50	CHRU - Hôpital du Haut Lévêque	Pessac	France	33604
51	Centre Hospitalier Lyon sud	Pierre - Bénite cedex	France	69495
52	CHRU - Hôpital Jean Bernard	Poitiers	France	86021
53	Centre Hospitalier de la région d'Annecy	Pringy	France	74374
54	Hôpital R.Debré	Reims	France	51092
55	CHRU - Hôpital de Pontchaillou	Rennes	France	35033
56	CHRU - Hôpital Sud	Rennes	France	35056
57	Centre Henri Becquerel	Rouen	France	76038
58	Groupe Hospitalier Sud Réunion	SAINT-PIERRE cedex	France	97448
59	Centre René Huguenin	St Cloud	France	92210
60	Centre Hospitalier Yves le Foll	St-Brieuc cedex 1	France	22 027
61	Centre Hospitalier Départemental - La réunion St Denis	St-denis	France	97 405
62	Institut de Cancérologie de la Loire	St-priest-en-jarez	France	42 271
63	Hôpitaux Universitaires de Strasbourg	Strasbourg	France	67091
64	University Hospital of Toulouse, Purpan	Toulouse	France	31059 Cedex 9
65	CHRU - Hôpital Bretonneau	Tours	France	37044
66	Centre Hospitalier de Valence	Valence	France	26953
67	CH Bretagne Atlantique Vannes et Auray	Vannes cedex	France	56017
68	Institut Gustave Roussy	Villejuif cedex	France	94 805