Newly diagnosed Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Revlimid
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5
Sponsors
Memorial Sloan Kettering Cancer center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Newly diagnosed patients with histologically confirmed MM based on the following criteria: -Clonal plasma cells in the bone marrow -Measurable disease within the past 4 weeks defined by any one of the following: - Serum monoclonal protein = 1.0 g/dL Urine monoclonal protein >200 mg/24 hour Involved serum immunoglobulin free light chain > 10 mg/dL AND abnormal kappa/lambda ratio •Evidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder meeting at least one of the following: -Hypercalcemia: serum calcium >0.25 mmol/L (> 1 mg/dL) above upper limit of normal or = 2.75 mmol/L (11 mg/dL) -Anemia: hemoglobin value 2 g/dL below lower limit of normal -Bone disease: = 1 lytic lesions on skeletal X-ray, CT, or PET-CT. For patients with 1 lytic lesion, bone marrow should demonstrate =10% clonal plasma cells -Clonal bone marrow plasma cell percentage =60% Involved/un-involved serum free light chain ratio =100 and involved free light chain >100 mg/L. - > 1 focal lesion on magnetic resonance imaging study (lesion must be >5 mm) in size •Creatinine Clearance = 60 ml/min. CrCl can be measured or estimated using Cockcroft-Gault method, MDRD, or CKD-EPI formulae •Age = 18 years at the time of signing the informed consent documentation. Age limit of = 75 years for Cohort 3 patients. •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 •Absolute neutrophil count (ANC) = 1.0 K/uL, hemoglobin = 8 g/dL, and platelet count = 75 K/uL, unless if cytopenias are deemed to be due disease at discretion of clinical investigator. Transfusions and growth factors are permissible. •Adequate hepatic function, with bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 231
Exclusion criteria
Exclusion criteria: -Patients receiving >1 cycle of prior treatment or concurrent systemic treatment for multiple myeloma -Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with current or prior corticosteroids is permitted -Bisphosphonates are permitted -Concurrent or prior treatment with corticosteroids for indications other than multiple myeloma is permitted -Prior treatment with radiotherapy is permitted -Prior Multiple Myeloma treatment for smoldering myeloma such as IMIDs and mABs is permitted with a washout period of 2weeks from last dose. Smoldering patients previously treated with carfilzomib are excluded. -Patients with measurable disease who received up to one cycle of any therapy within 60 days with a washout period of 2 weeks from last dose (on a trial or outside a trial) are eligible •Plasma cell leukemia •POEMS syndrome •Amyloidosis •Has known chronic obstructive pulmonary disease with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal (note that FEV1 testing is required for subjects suspected of having chronic obstructive pulmonary disease and subjects must be excluded if FEV1 <50% of predicted normal). •Pregnant or lactating females. Because there is a potential risk for adverse events nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide. These potential risks may also apply to other agents used in this study. •Uncontrolled hypertension or diabetes •Active hepatitis B or C infection •Subject is: -Seropositive for human immunodeficiency virus (HIV) -Seropositive for hepatitis B -Seropositive for hepatitis C •Has significant cardiovascular disease with NYHA Class III or IV symptoms, EF<40% or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 6 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination. Echocardiogram will be performed during screening evaluation. •Pulmonary hypertension •Has refractory GI disease with refractory nausea/vomiting, inflammatory bowel disease, or bowel resection that would prevent absorption of oral agents •Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements •Significant neuropathy =Grade 3 or Grade 2 neuropathy with pain at baseline •Contraindication to any concomitant medication, including antivirals or anticoagulation. •Major surgery within 3 weeks prior to first dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the rates of MRD negativity for patients who receive VRD (Arm A) to patients who receive KRD (Arm B) and for patients who received VRD (Arm A) to patients who received KRD + DARA (Arm C). ;Secondary Objective: 1. To compare overall survival, progression-free survival, and event-free survival in patients achieving PR or less within the first 4 cycles of therapy, across the treatment arms (Arm A vs Arm B, Arm A vs Arm C). 2. To compare the rates of PR or better, VGPR or better, CR and sCR across the treatment arms (Arm A vs Arm B, Arm A vs Arm C). 3. To compare the rate of MRD-negativity as a best response after the completion of eight cycles of therapy across the treatment arms (Arm A vs Arm B, Arm A vs Arm C). In addition, to compare the rate of MRD-negativity 12 months after randomization across the treatment arms (Arm A vs Arm B, Arm A vs Arm C). 4. To compare the safety and tolerability of the three treatment arms 5. To compare MRD-assesments in bone marrow versus blood with different techniques ;Primary end point(s): The primary endpoint of the study is MRD negativity after eight cycles of theraphy;Timepoint(s) of evaluation of this end point: After 8 cycles of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include evaluation of safety and tolerability of the three treatment arms, and to compare the response rates, progression-free survival, overall-survival. MRd and Next generation sequencing will also be investigated as a secondary endpoint. ;Timepoint(s) of evaluation of this end point: Safety and tolerability will be followed from Study start until 1 month after completed treatment. Overall response, progression-free survival, overall survival will be followed throughout the Study. | — |
Countries
Sweden, United States
Contacts
Public ContactMarkus Hansson
Skåne University Hospital
Outcome results
None listed