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

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ClinicalTrials.gov Identifier: NCT01191060
Recruitment Status : Completed
First Posted : August 30, 2010
Last Update Posted : April 18, 2019
Sponsor:
Collaborators:
Dana-Farber Cancer Institute
Celgene Corporation
Janssen-Cilag Ltd.
Information provided by (Responsible Party):
University Hospital, Toulouse

Tracking Information
First Submitted Date  ICMJE April 16, 2010
First Posted Date  ICMJE August 30, 2010
Last Update Posted Date April 18, 2019
Actual Study Start Date  ICMJE October 2010
Actual Primary Completion Date November 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2015)
Progression Free Survival [ Time Frame: up to 4 years ]
To compare progression-free survival (PFS) between the Arm A and Arm B up to 4 years or until progression
Original Primary Outcome Measures  ICMJE
 (submitted: August 27, 2010)
Progression Free Survival [ Time Frame: up to 4 years or until progression ]
To compare progression-free survival (PFS) between the Arm A and Arm B.
Change History Complete list of historical versions of study NCT01191060 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2012)
  • Response Rates [ Time Frame: up to 4 years ]
    -Response rates (RR) between the two arms up to 4 years or until progression
  • Time To Progression [ Time Frame: up to 4 years ]
    Time to progression (TTP) between the two arms up to 4 years or until progression
  • Toxicity comparison [ Time Frame: up to 4 years ]
    Toxicity comparison between the two arms randomization up to 4 years or until progression
  • Genetic prognostic groups definition [ Time Frame: 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. [ Time Frame: up to 4 years ]
    Best treatment examination in each GEP-defined prognostic group. from randomization up to 4 years or until progression
Original Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2010)
  • Response Rates [ Time Frame: up to 4 years or until progression ]
    -Response rates (RR) between the two arms
  • Time To Progression [ Time Frame: up to 4 years or until progression ]
    -Time to progression (TTP) between the two arms
  • Toxicity comparison [ Time Frame: from randomization up to 4 years or until progression ]
    -Toxicity comparison between the two arms
  • Genetic prognostic groups definition [ Time Frame: from randomization up to 4 years or until progression ]
    -Genetic prognostic groups definition (evaluated by gene expression profiling-GEP)
  • Best treatment examination in each GEP-defined prognostic group. [ Time Frame: from randomization up to 4 years or until progression ]
    Best treatment examination in each GEP-defined prognostic group.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Comparing Conventional Dose Combination RVD to High-Dose Treatment With ASCT in the Initial Myeloma up to 65 Years
Official Title  ICMJE 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
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).
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myeloma
Intervention  ICMJE
  • 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®)
  • 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®)
Study Arms  ICMJE
  • 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)

    Intervention: Drug: Lenalidomide, Bortezomib
  • 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)
    Intervention: Drug: Lenalidomide, Bortezomib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 27, 2010)
700
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 30, 2018
Actual Primary Completion Date November 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01191060
Other Study ID Numbers  ICMJE 09 110 01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Toulouse
Study Sponsor  ICMJE University Hospital, Toulouse
Collaborators  ICMJE
  • Dana-Farber Cancer Institute
  • Celgene Corporation
  • Janssen-Cilag Ltd.
Investigators  ICMJE
Principal Investigator: MICHEL ATTAL, MD PhD University Hospital of Toulouse
PRS Account University Hospital, Toulouse
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP