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
Sponsors
Polish Myeloma Consortium
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Patients who completed single autologous stem cell transplant after completion of at most 2 induction regimens (excluding dexamethasone alone) and are in at least stable disease prior to randomization in the first 100 days after stem cell transplantation. 2)Patient must be within 12 months of initiation of induction therapy and must have had not more than 2 prior induction regimens 3)Bone marrow specimen will be required at study entry; available DNA sample from pre-induction BM will be used for calibration step for MRD evaluation by gene sequencing. 4)Males and females =18 years of age 5)ECOG performance status of 0-1 6)Adequate hepatic function, with bilirubin =1.5 x ULN and aspirate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 xULN 7)ANC =1.0 x 109/L, hemoglobin =8 g/dL, platelet count =75 x 109/L. 8)Calculated creatinine clearance (by Cockroft-Gault) =50 ml/min or serum creatinine below 2 g/dL 9)Females of childbearing potential (FCBP) must have 2 negative pregnancy tests (sensitivity of at least 50 mIU/mL) prior to initiating lenalidomide. The first pregnancy test must be performed within 10-14 days before and the second pregnancy test must be performed within 24 hours before lenalidomide is prescribed for Cycle 1 (prescriptions must be filled within 7 days). 10)FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 28 days before starting lenalidomide; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study. 11)Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy. 12)All study participants must be consented to and registered into the mandatory RevlimidREMS® program and be willing and able to comply with the requirements of RevlimidREMS®. 13)Voluntary written informed consent 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 160 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1)Patients who have had more than 12 months of prior therapy. Patients outside of this window may be considered for inclusion. Please contact the Sponsor’s representative in Poland or the Lead Primary Investigator as appropriate on a case-by-case basis 2)Patients who progressed after initial therapy. a)Subjects whose therapy changed due to suboptimal response, intolerance, etc., remain eligible, provided they do not meet criteria for progression. b)No more than two regimens for induction will be allowed, excluding dexamethasone alone. 3)Potential subjects with evidence of progressive disease as per IMWG criteria 4)Patients who have already started or received post-transplant maintenance or consolidation regimen 5)Patients not able to tolerate lenalidomide or carfilzomib or dexamethasone 6)POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 7)Plasma cell leukemia 8)Waldenström’s macroglobulinemia or IgM myeloma 9)Peripheral neuropathy = Grade 2 at screening 10)Diarrhea > Grade 1 in the absence of antidiarrheals 11)CNS involvement 12)Pregnant or lactating females 13)Radiotherapy within 14 days before randomization. Seven days may be considered if to single area 14)Major surgery within 3 weeks prior to first dose 15)Myocardial infarction within 3 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities 16)Prior or concurrent deep vein thrombosis or pulmonary embolism 17)Rate-corrected QT interval of electrocardiograph (QTc) > 470 msec on a 12-lead ECG during screening 18)Uncontrolled hypertension or diabetes 19)Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose 20)Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. 21)Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone 22)Any clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To determine the rate of MRD-negative disease at 6, 12, 18, 24, and 36 months after randomization To compare the efficacy (rate of PR, VGPR, CR, and sCR) of KRd vs. Lenalidomide alone after randomization To evaluate the safety and tolerability of KRd compared to lenalidomide alone ;Primary end point(s): The comparison of PFS rates between patients treated with KRd vs. R alone after SCT will be achieved by measuring the time to progressive disease or death as defined by IMWG (International Myeloma Working Group) criteria. ;Timepoint(s) of evaluation of this end point: Time to progression or death will be calculated from the date of first treatment until progression assessed by the Investigator according to IMWG (International Myeloma Working Group) criteria or death.;Main Objective: To compare progression free survival (PFS) between KRd (Kyprolis, Revlimid, Dexamethasone) and lenalidomide (Revlimid) arm after randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Determine the correlation between the MRD status at 6, 12, 18, 24, and 36 months and median PFS in both arms. Determine rates of improvement of the depth of response by at least one category according to IMWG response criteria. (For example, an improvement from very good partial response (VGPR) to near complete response (nCR) or better than nCR including conversion from CR to MRD negative disease [overall response]) at 6 and 12 months. Compare overall survival between arms. Determine the duration of MRD-negative disease. Safety and tolerability of experimental arm vs. control.;Timepoint(s) of evaluation of this end point: MRD evaluation at 6, 12, 18, 24, and 36 months. Determine the depth of disease response at 6 and 12 months. Overall Survival defined as time from first study treatment dose to death due to any cause. | — |
Countries
Poland, United States
Contacts
Public ContactPolish Myeloma Consortium
Polish Myeloma Consortium
Outcome results
None listed