Myeloma, Multiple Myeloma MedDRA version: 12.0 Level: LLT Classification code 10028228 Term: Multiple myeloma MedDRA version: 12.0 Level: LLT Classification code 10028566 Term: Myeloma
Conditions
Sponsors
CHU de TOULOUSE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligibility Criteria for registration • 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 labs peformed within 21 days of study entry: ? Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven plasmacytoma ? Monoclonal protein (M-protein) present in the serum and/or urine. If no monoclonal protein is detected (non-secretory) disease, then > 30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma required ? 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/l or upper limit of normal ? [R] Renal insufficiency, defined as serum creatinine > 2 mg/dl ? [A] Anemia, defined as hemoglobin 30% plasma cells are required in the bone marrow. ? 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 symptomatic myeloma with organ damage related to myeloma as defined in section 3.1.1 with labs done within 21 days of study entry. • Participants must have myeloma that is measurable by either serum evaluation of the monoclonal component or by assay of free light chains (serum or urinary). 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 provided serum FLC ratio is abnormal. • Age between 18 and 65 years at the time of signing the informed consent form. • ECOG performance status 60%, see Appendix V). • Negative HIV blood test within 21 days of study entry. HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for 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. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated. 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* • Premature ovarian failure confirmed by a specialist gynaecologist • Previous bilateral salpingo-oophorectomy, or hysterectomy • XY genotype, Turner syndrome, uterine agenesis. *Amenorrhoea following cancer therapy does not rule out childbearing potential. Female subjects of childbearing potential must follow the recommandations as precognized in the protocol. Male subjects must - Agree to use condoms throughout study drug therapy, during any dose interruption and for one week after cessation of study therapy if their partner is of childbearing potential and has no contraception. - Agree not to donate semen during study drug therapy and for one week after end of study drug therapy. All subjects must - Agr
Exclusion criteria
Exclusion criteria: All labs should be done within 21 days of study entry. • Participant must not have been 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 entry in the study is observed. Similarly, the dose of corticosteroids received by the participant prior to study entry as part of any initial therapy should not exceed the equivalent of 160 mg of dexamethasone over a two-week period. • Primary amyloidosis (AL) or myeloma complicated by amylosis. • Participants may not be receiving any other study 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 2mg/dL and AST (SGOT), ALT (SGPT), or alkaline phosphotase > 2x ULN • Renal insufficiency, defined as serum creatinine > 2.5 mg/dL and/or creatinine clearance Grade 2 on clinical examination. • Mental illness likely to interfere with participation in the study and adults under juridical protection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare progression-free survival (PFS) between Arm A and Arm B ;Secondary Objective: • To compare the response rates (RR) between the two arms • To compare time to progression (TTP) between the two arms • To compare the overall survival (OS) between the two arms • To compare the toxicity between the two arms • To define genetic prognostic groups evaluated by gene expression profiling (GEP) • To examine the best treatment in each Gene Expression Profile-defined prognostic group ;Primary end point(s): The primary objective of this randomized phase III study is to compare the progression-free survival (PFS) of Arms A (conventional dose arm) and Arm B (high dose therapy arm) in newly diagnosed myeloma patients who have completed 1 cycle of RVD. PFS is defined as the time from randomization until progression or death from any cause. Patients alive without confirmed progression will be censored at the time of the last disease evaluation. Deaths without progression are counted as failures even if they occur long after the last disease evaluation. Patients are stratified by county (US vs. IFM), poor vs. standard cytogenetic risk factors and ISS (Stage I vs. II vs. III). Patients will be randomized equally to the two arms using permuted blocks within stratification combinations. Endpoint definitions Duration of overall response: The duration of overall response is measured as the time from initiation of first response to first documentation of disease progression or death. Patients who have not progressed or died are censored at the date last known progression-free. Duration of overall complete response: The duration of overall CR is measured as the time from initiation of CR to first documentation of disease progression or death. Patients who have not progressed or died are censored at the date last known progression-free . Progression-Free Survival (PFS): the primary endpoint in this study. PFS is defined as the time from initiation of the fi | — |
Countries
Belgium, France
Outcome results
None listed