Frontline Therapy in de Novo Multiple Myeloma Patients Under 65 (IFM2008)

This study has been completed.
Sponsor:
Collaborators:
Celgene Corporation
Janssen-Cilag Ltd.
Information provided by (Responsible Party):
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT01206205
First received: September 17, 2010
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

The purpose of this Phase 2 study is to evaluate the efficacy and safety of treatment with bortezomib, lenalidomide and dexamethasone in patients with untreated multiple myeloma. This study will evaluate whether the addition of lenalidomide to bortezomib and dexamethasone will increase the Complete Response (CR)/ very good partial response (VGPR) rate before and after High Dose Therapy (HDT) with ASCT.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide, Bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: IFM2008: Frontline Therapy in de Novo Multiple Myeloma Patients Under 65, (a Phase 2 Multicenter Trial)

Resource links provided by NLM:


Further study details as provided by University Hospital, Toulouse:

Primary Outcome Measures:
  • Evaluation of the best response after consolidation [ Time Frame: 6 to 8 months after start of induction for each patient = after consolidation therapy for all patients ] [ Designated as safety issue: Yes ]
    Evaluate the best response achieved , according to the IMWG uniform criteria, after consolidation treatment.


Secondary Outcome Measures:
  • Response Evaluation after 3 cycles [ Time Frame: 6 to 8 months after start of induction for each patient = after consolidation therapy for all patients ] [ Designated as safety issue: Yes ]
    Evaluate the complete and very good partial response rates of the combination of bortezomib, lenalidomide and dexamethasone in newly diagnosed multiple myeloma patients after 3 cycles.

  • Safety and tolerability : number and nature of Adverse Events [ Time Frame: 6 to 8 months after start of induction for each patient = after consolidation therapy for all patients ] [ Designated as safety issue: Yes ]
    Determine the safety and tolerability of the drug combination in this patient populations.

  • Stem Cells Collection [ Time Frame: 6 to 8 months after start of induction for each patient = after consolidation therapy for all patients ] [ Designated as safety issue: No ]
    Evaluate the faisability and quality of the peripheral stem cells collection.

  • Response After HDT-ASCT and 2 cycles [ Time Frame: 6 to 8 months after start of induction for each patient = after consolidation therapy for all patients ] [ Designated as safety issue: Yes ]
    Evaluate the complete and very good partial response rates 2 months after HDT with ASCT and after 2 cycles of consolidation treatment.

  • Progression Free Survival [ Time Frame: 6 to 8 months after start of induction for each patient = after consolidation therapy for all patients ] [ Designated as safety issue: Yes ]
    Evaluate the progression free survival, the overall survival, time to progression and duration of response.


Enrollment: 31
Study Start Date: August 2009
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide, Bortezomib

3 induction cycles of bortezomib, lenalidomide and dexamethasone (VRD) followed by high dose melphalan and autologous stem cell transplantation.

Two months after haematological recovery, patients will receive 2 consolidation cycles of VRD and maintenance therapy for 1 year with lenalidomide.

Drug: Lenalidomide, Bortezomib

Induction:

3 cycles of 21 days of Dexamethasone : 40 mg/j, days 1, 8 et 14 Bortezomib (Velcade®) : 1,3 mg/m2/d, days 1, 4, 8, et 11 Lenalidomide (Revlimid®) :25 mg/d, days 1 to 14

Consolidation (2 months After ASCT):

2 cycles of 21 days of Lenalidomide (Revlimid®) 25 mg/j, days 1 à 14 Bortezomib (Velcade®) 1,3 mg/m2/d, days 1, 4, 8, et 11 Dexamethasone 40 mg/j, days 1, 8 et 14

Maintenance Phase:

3 to 8 weeks after consolidation. Cycle length: 28 days Lenalidomide (Revlimid®) 10 mg/d until 12 months

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

Detailed Description:

Patients will receive 3 induction cycles of bortezomib, lenalidomide and dexamethasone (VRD) followed by high dose melphalan and autologous stem cell transplantation. Two months after haematological recovery, patients will receive 2 consolidation cycles of VRD and maintenance therapy for 1 year with lenalidomide

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients diagnosed with multiple myeloma based on standard diagnostic criteria or by the new International Myeloma Foundation 2003 Diagnostic Criteria
  • Subjects must have symptomatic myeloma or asymptomatic myeloma with myeloma-related organ damage
  • Subjects must have measurable disease requiring systemic therapy.
  • Male or female subject 18 years of age or older
  • Karnofsky Performance Status score of ≥50% (Eastern Cooperative Oncology Group Performance Status score ≤2)
  • Voluntary written informed consent must be given before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to therapy. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (1 highly effective method and 1 additional effective method) used at the same time, beginning at least 4 weeks before initiation of Revlimid treatment. Women must also agree to ongoing pregnancy testing
  • Men must agree to not father a child and agree to use a latex condom during therapy and for 4 weeks after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential.

Exclusion Criteria:

  • Subjects must not have been treated previously with any systemic therapy for multiple myeloma. Prior treatment with corticosteroids or radiation therapy does not disqualify the subject (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in a 2-week period). Two weeks must have elapsed since the date of the last radiotherapy treatment. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.
  • AL amylo
  • ≥Grade 2 peripheral neuropathy on clinical examination within 14 days before enrollment
  • Renal insufficiency (serum creatinine >2.5 mg/dL)
  • Evidence of mucosal or internal bleeding and/or platelet refractory
  • Platelet count <70,000 per µL
  • ANC < 1000 cells/mm3
  • AST or ALT greater than or equal to 2 x ULN
  • Total bilirubin >3 × ULN
  • Myocardial infarction within 6 months prior to enrollment according to NYHY Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • Clinically relevant active infection or serious co-morbid medical conditions
  • Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer
  • Female subject who is pregnant or breast-feeding
  • Serious medical or psychiatric illness likely to interfere with participation in study
  • Uncontrolled diabetes mellitus
  • Known HIV infection
  • Known active hepatitis B or C viral infection
  • Known intolerance to steroid therapy
  • History of allergy to any of the study medications, their analogues, or excipients in the various formulations
  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: NCT01206205

Locations
France
Centre François Baclesse
Caen, cedex 5, France, 14076
University Hospital of Dijon, Hôpital des Enfants
Dijon, France, 21000
University Hospital of Grenoble, Hôpital A.Michallon, BP 217 X
Grenoble Cedex 09, France, 38043
University Hospital Of Lille, Hôpital Claude Huriez
Lille Cedex, France, 59037
Institut Paoli Calmette
Marseille Cedex, France, 13273
University Hospital of Bordeaux, "Hôpital du Haut Lévêque "
Pessac, France, 33604
University Hospital of Toulouse, Purpan
Toulouse, France, 31059
Hôpital Bretonneau, Tours
Tours Cedex, France, 37044
Hôpitaux de Brabois Nancy
Vandoeuvre cedex, France, 54511
Sponsors and Collaborators
University Hospital, Toulouse
Celgene Corporation
Janssen-Cilag Ltd.
Investigators
Principal Investigator: Michel ATTAL, MD 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: NCT01206205     History of Changes
Other Study ID Numbers: 0805603
Study First Received: September 17, 2010
Last Updated: June 11, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Toulouse:
De novo Multiple Myeloma
Bortezomib
Lenalidomide
induction therapy
consolidation therapy
maintenance therapy
High dose therapy
frontline therapy including new drugs and high dose therapy

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014