A Randomized Phase III Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib and Dexamethasone (RVD) to High-Dose Treatment with Peripheral Stem Cell Transplant in the Initial Management of Myeloma in Patients up to 65 Years of Age (IFM/DFCI 2009) - IFM/DFCI 2009

Phase 1

Conditions: Myeloma, Multiple Myeloma
MedDRA version: 18.1 Level: LLT Classification code 10028566 Term: Myeloma System Organ Class: 100000004864
MedDRA version: 18.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2009-016871-32-BE

Lead Sponsor: CHU de TOULOUSE

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 700

Inclusion Criteria

•All laboratory assessments should be performed within 21 days of
initiation of protocol therapy:
• Participants must have a diagnosis of MM, according to International
Myeloma Foundation 2003 Diagnostic Criteria. According to these
criteria, all three of the following must be met with screening tests
performed within 21 days of initiation of protocol therapy:
? Monoclonal plasma cells in the bone marrow > 10% (or proven
plasmocytic infiltration in bone marrow biopsy)and/or presence of a
biopsy-proven plasmacytoma
? Monoclonal protein (M-protein) present in the serum and/or urine.
? Myeloma-related organ dysfunction (1 or more) of the following. A
variety of other types of end-organ dysfunctions can occasionally occur
and lead to a need for therapy:
[C] Calcium elevation in the blood, defined as serum calcium > 10.5
mg/dl or upper limit of normal
[A] Anemia, defined as hemoglobin <10 g/dl or 2 g < normal
[B] Lytic bone lesions or osteoporosis. If a solitary (biopsy-proven)
plasmacytoma or osteoporosis alone (without fractures) are the sole
defining criteria, then > 30% plasma cells are required in the bone
marrow or proven plasmocytic infiltration in bone marrow biopsy..
Note: These criteria identify Stage IB and Stages II and III A/B
myeloma by Durie-Salmon stage. Stage IA becomes smoldering or
indolent myeloma.
• Participants must have documented symptomatic myeloma with
organ damage related to myeloma as defined above with laboratory
assessments performed within 21 days of initiation of protocol therapy.
• Participants must have myeloma that is measurable by either serum
or urine evaluation of the monoclonal component or by assay of serum
free light chains. Measurable disease is defined as one or more of the
following: serum M-protein = 1 g/dl, urine M-protein = 200 mg/24 h,
and/or serum FLC assay: involved FLC level = 10 mg/dl with abnormal
serum FLC ratio.
• Age between 18 and 65 years at the time of signing the informed
consent form.
• ECOG performance status =2 (Karnofsky =60%, see Appendix IV).
• Negative HIV blood test within 21 days of initiation of protocol
therapy. HIV-positive individuals on combination antiretroviral therapy
are ineligible because of the potential for pharmacokinetic (PK)
interactions with lenalidomide, bortezomib and/or dexamethasone. In
addition, these individuals are at increased risk of lethal infections when
treated with marrow-suppressive therapy.
o Criteria for women of non-childbearing potential
A female subject or a female partner of a male subject is considered to
have childbearing potential unless she meets at least one of the
following criteria:
• Age = 50 years and naturally amenorrhoeic for = 1 year*
• Premat

Exclusion Criteria

All laboratory assessments should be performed within 21 days of initiation of protocol therapy:
• Participant treated with any prior systemic therapy. 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 is
observed. Similarly, the dose of corticosteroids received by the participant as part of any initial therapy should
not exceed the equivalent of 160 mg of dexamethasone over a two-week period before initiation of protocol
therapy (see Appendix V for equivalence table).
• Primary amyloidosis (AL) or myeloma complicated by amylosis.
• Participants receiving any other investigational agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor
prognosis and because they often develop progressive neurologic dysfunction that would confound the
evaluation of neurologic and other adverse events.
• Poor tolerability or known allergy to any of the study drugs or compounds of similar chemical or biologic
composition to lenalidomide, bortezomib and/or dexamethasone.
• Participants with platelet level <50,000/mm3. Transfusion within 7 days of screening is not allowed to meet
platelet eligibility criteria
• Participants with an absolute neutrophil count (ANC) <1000/uL. Growth factor within 7 days of screening is
not allowed to meet ANC eligibility criteria.
• Participants with hemoglobin level < 8.0 g/dL. Transfusion may be used to meet hemoglobin eligibility criteria.
• Hepatic impairment, defined as bilirubin > 1.5 ? Institutionnal ULN Total Bilirubin (Patients with benign
hyperbilirubinemia (e.g., Gilbert’s syndrome) are eligible ) or AST (SGOT), or ALT (SGPT), or alkaline
phosphatase = 2x ULN
• Renal insufficiency, defined as serum creatinine > 170 µmol and/or creatinine clearance < 50 mL/min (either
actual or calculated values may be used). The Cockgroft-Gault formula should be used for calculating creatinine
clearance values:
(140-age) x Body mass (kg) x 0.85 (female) or 1.0 (male)
serum creat (mg/dL) x 72
• Respiratory compromise, defined as ventilation tests with DLCO < 50%
• Participant with clinical signs of heart or coronary failure, or evidence of left ventricular ejection fraction
(LVEF) < 40%. Participant 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 conductive 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, poor

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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