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. Newly diagnosed, previously untreated myeloma requiring systemic chemotherapy per IMWG criteria: • Patients must have received no prior chemotherapy for this disease; patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis); prior steroid treatment is allowed provided treatment was not more than 2 weeks in duration and = 160 mg dexamethasone; patients must not have received any prior treatment with bortezomib or lenalidomide 2. Both transplant and non-transplant candidates are eligible. Transplant candidates must agree at time of consent to defer transplant to the end of study treatment. If patient proceeds to transplant, they will come off study. 3. Diagnosis of symptomatic multiple myeloma as per current IMWG uniform criteria prior to initial treatment 4. Monoclonal plasma cells in the BM 10% or presence of a biopsy-proven plasmacytoma 5. Measurable disease, prior to initial treatment as indicated by one or more of the following: • Serum M-protein = 1 g/dL • Urine M-protein = 200 mg/24 hours • Involved serum free light chains = 10 mg/dL provided that free light chain ratio is abnormal • If serum protein electrophoresis is felt to be unreliable for routine M-protein measurement, then quantitative immunoglobulin levels are acceptable 6. Bone marrow specimen will be required at study entry; available DNA sample from pre-treatment BM will be used for calibration step for MRD evaluation by gene sequencing. 7. Males and females = 18 years of age 8. ECOG performance status of 0-2 9. Adequate hepatic function, with bilirubin = 1.5 x ULN and aspirate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 xULN 10. ANC = 1.0 x 109/L, hemoglobin = 8 g/dL, platelet count = 75 x 109/L. 11. Calculated creatinine clearance (by Cockroft-Gault) = 50 mL/min or serum creatinine below 2 g/dL 12. Female of child bearing 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). 13. 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 30 days after discontinuation from the study. 14. 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 90 days following discontinuation from the study even if he has undergone a successful vasectomy. 15. All study participants in the US and EU countries (excluding Poland) must be consented to and registered into the mandatory Revlimid REMS® program and be willing and able to comply with the requirements of Revlimid REMS®. 16. Subjects must comply with pregnancy prevention and counseling 17. 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 175 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: Patients meeting any of the following exclusion criteria are not eligible to enroll in this study. 1. Frail, non-transplant candidates, per modified IMWG frailty score (age not counted as a scoring factor) 2. Non-secretory or hyposecretory multiple myeloma, prior to initial treatment defined as Grade 1 in the absence of antidiarrheals 12. CNS involvement 13. Patients who cannot undergo or unwilling to take thromboprophylaxis 14. Uncontrolled or symptomatic angina, arrhythmia, hypertension, CHF, EF 470 msec on a 12-lead ECG during screening 21. Uncontrolled diabetes 22. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose 23. 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 or are asymptomatic chronic carriers of HBV are eligible. 24. 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 25. 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 |
|---|---|
| Main Objective: To compare the MRD-negative complete response status at 12 months after randomization and PFS;Secondary Objective: •To compare the status of MRD-negative disease at 8 and 24 months after randomization between the KRd and VRd arms. •To evaluate the duration of MRD-negative status between the two arms •To compare the MRD-negative complete response status as best response between two arms. •To evaluate the efficacy (rate – ORR - and sustainability -DOR - of PR, VGPR, CR, and sCR) across entire treatment in high risk and low risk patients and as best response of KRd vs. VRd after randomization •To determine rates of improvement of the depth of response by at least one category according to IMWG response criteria. •To compare overall survival •To evaluate the safety and tolerability of KRd compared to VRd ;Primary end point(s): The MRD-negative complete response status at 12 months by NGS and PFS defined as the time to progressive disease or death as defined by IMWG criteria;Timepoint(s) of evaluation of this end point: Time to progression or death will be calculated from the data of first treatment until progression assessed by Investigator according to IMWG (International Myeloma Working Group) criteria or death. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The MRD-negative status in each study arm at 8and 24 months • Duration of MRD-negative status. • MRD-negative complete response • Comparing rate of PR or better, VGPR or better, CR or better, or sCR at 8, 12, 24, 36, 48, and 60 months and as best response between the two 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 specified landmark timepoints. • To compare overall survival. • Safety and tolerability of KRd vs. VRd;Timepoint(s) of evaluation of this end point: • GEP, proteomics, RNASeq, and gene sequencing studies will be conducted on pre-treatment patient samples to evaluate the correlation between treatment outcome, using KRd or VRd, and pre-treatment patient profile • MRD status at 36, 48 and 60 months in both arms | — |
Countries
Finland, Norway, Poland, United States
Contacts
Public ContactPolish Myeloma Consortium
Polish Myeloma Consortium
Outcome results
None listed