Newly diagnosed symptomatic multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Revlimid® 5 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration numb
Sponsors
Ruprecht-Karls-University Heidelberg, Medical Faculity, represented by University Hospital Heidelberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Confirmed diagnosis of untreated multiple myeloma requiring systemic therapy (diagnostic criteria (IMWG updated criteria (2014)). For some patients systemic therapy may be required though these diagnostic criteria are not fulfilled. In this case the GMMG study office has to be consulted prior to inclusion. - Patient is eligible for high dose therapy and autologous stem cell transplantation. - Measurable disease, defined as any quantifiable monoclonal protein value, defined by at least one of the following three measurements: • Serum M-protein = 10g/l (for IgA = 5g/l) • Urine light-chain (M-protein) of = 200 mg/24 hours • Serum FLC assay: involved FLC level = 10 mg/dl and abnormal sFLC ratio - Age 18 - 70 years inclusive - WHO performance status 0-2 - Negative pregnancy test at inclusion (women of childbearing potential) - For all men and women of childbearing potential: patients must be willing and capable to use adequate contraception during the complete therapy. Patients must agree on the requirements regarding the lenalidomide pregnancy prevention programme - All patients must: • agree to abstain from donating blood while taking lenalidomide and for 28 days following discontinuation of lenalidomide therapy • agree not to share study drug lenalidomide with another person and to return all unused study drug to the investigator or pharmacist - Ability of patient to understand character and individual consequences of the clinical trial - Provide written informed consent (must be available before enrolment in the trial) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 530 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 132
Exclusion criteria
Exclusion criteria: - Patient has known hypersensitivity (or contraindication) to dexamethasone, sucrose histidine (as base and hydrochloride salt), boron, mannitol, and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids or H2 blockers that would prohibit further treatment with these agents. - Systemic AL amyloidosis (except for AL amyloidosis of the skin or the bone marrow) - Plasma cell leukemia - Previous chemotherapy or radiotherapy during the past 5 years except local radiotherapy in case of local myeloma Progression or benign diseases, such as non-malignant thyroid diseases. (Note: patients may have received a cumulative dose of up to 160 mg of dexamethasone or equivalent as emergency therapy.) Previous therapy due to smouldering myeloma may be acceptable. In this case the GMMG study office has to be consulted prior to inclusion. - Severe cardiac dysfunction (NYHA classification III-IV) - Significant hepatic dysfunction (ASAT and/or ALAT = 3 times normal level and/or serum bilirubin = 1.5 times normal level if not due to hereditary abnormalities as Gilbert’s disease), unless related to myeloma. - Patients with active or history of hepatitis B or C (Prior hepatitis B may be acceptable if an adequate prophylaxis is being implemented during the course of the study.) - HIV positivity - Patients with active, uncontrolled infections - Patients with severe renal insufficiency (Creatinine Clearance 14 mg/dl (> 3.5 mmol/l) - Unable or unwilling to undergo thromboprophylaxis - Pregnancy and lactation - Participation in other clinical trials. This does not include long-term follow-up periods without active drug treatment of previous studies during the last 6 months. - Prisoners or subjects who are legally institutionalized, or those unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions. No patients will be allowed to enrol in this trial more than once.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: (1) to compare induction therapy without isatuximab (arm IA) versus induction therapy with isatuximab (arm IB) regarding the MRD negativity after induction (assessed by flow cytometry). (2) to compare maintenance therapy without isatuximab (arm IIA) with maintenance therapy with isatuximab (arm IIB) regarding the progression-free survival (PFS), defined as time from 2nd randomization (prior to maintenance therapy) to progression or death from any cause whichever occurs first.;Secondary Objective: Key Sec Objective: - to assess and compare the four treatment arms (IA-IIA, IA-IIB, IB-IIA, IB-IIB) regarding PFS, defined as time from 1st randomization to progression or death from any cause whichever occurs first Further Sec Objectives: - To assess the treatment effect of the induction phase regarding PFS from 1st randomization - Overall survival (OS) from 1st/2nd randomization - Complete response (CR) rates after induction therapy, high dose therapy and during/after maintenance therapy - MRD negativity after high dose therapy, during and after 3 years of maintenance treatment (flow cytometry) - Sustained MRD negativity for =6 months / =12 months - Best response to treatment during the trial - PFS 2 (PFS after next line of therapy) from 2nd randomization - Toxicity during induction and maintenance: adverse events of CTC grade = 3 (and specific AE of CTC grade = 2) and serious AE - Quality of life assessment - Pharmacokinetics of isatuximab in combination with RVd or Rd ;Primary end point(s): (1) minimal residual disease (MRD) negativity after induction (assessed by flow cytometry; sensitivity 1e-5), defined as proportion of patients with negative MRD after induction. (2) progression-free survival (PFS), defined as time from 2nd randomization (prior to maintenance) to progression or death from any cause whichever occurs first. ;Timepoint(s) of evaluation of this end point: Any time | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoint: - PFS, defined as time from 1st randomization (at study inclusion) to progression or death from any cause whichever occurs first. Further Secondary Endpoints: - To assess the treatment effect of the induction phase regarding PFS from 1st randomization. Induction treatment effect will be assessed by comparing a) the overall IA to IB (independently on 2nd randomization) and additionally by comparing the treatment arms IA-IIA to IB-IIA (induction treatment followed by lenalidomide maintenance). To assess the treatment effect of the induction phase regarding overall survival from 1st randomization. Comparisons will be done analogously to PFS from 1st randomization. - OS defined as time from 1st randomization and from 2nd randomization to time of death from any cause. Patients still being alive at the time of the analysis will be censored at the date last known to be alive. - Complete response (CR) rates. The analysis will be based on the CR rate which is the proportion of patients achieving complete response (CR) to treatment adjusted after removal of isatuximab interference in the relevant patient subpopulations. - MRD negativity after high dose therapy, during and after 3 years of maintenance treatment (flow cytometry) defined as the proportion of patients with negative MRD after high dose therapy, during and after 3 years of maintenance treatment (flow cytometry), respectively. - Sustained MRD-negativity, defined as the maintenance of MRD-negativity (assessed by NGF at a sensitivity of 1e-5) >=6 / >=12 months apart (after first occurrence of MRD negativity) - Best response to treatment during the trial (adjusted after removal of isatuximab interference in the relevant patient subpopulations) - PFS 2 (PFS after next line of therapy) from 2nd randomization - Quality of life Safety will be analysed including: - Toxicity (CTC grade = 3) during induction and maintenance therapy, respectively, measured by CTC-AE (v5.0). Fo | — |
Countries
Germany
Contacts
Public ContactGMMG Studiensekretariat
GMMG Study Office
Outcome results
None listed