Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Included in EMN02/HO95 trial - The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures. - Age = 18 years at the time of signing the informed consent form. - Able to adhere to the study visit schedule and other protocol requirements. - Documented diagnosis of multiple myeloma and measurable disease (serum M-protein = 10 g/L or urine M-protein = 200 mg/24 hours or abnormal FLC ratio with involved free light chain (FLC) > 100 mg/L) or proven plasmacytoma by biopsy); - At least prior anti-myeloma regimen according to the EMN02/HO95 trial and documented progression or refractory multiple myeloma as per the IMWG uniform response criteria (Durie, 2006) during or after the last anti-myeloma regimen. Induction therapy followed by autologous stem cell transplant (AutoSCT) and consolidation/ maintenance will be considered as one regimen. - Patients who have never achieved a response better than PD after at least 2 cycles of lenalidomide containing therapy or who progressed whilst on treatment. - Normal renal function with a Creatinine Clearance > 45mL/min according to the Modification of Diet in Renal Disease (MDRD) equation for estimation of Glomerular Filtration Rate (GFR) - WHO performance status score of 0, 1 or 2. - Patients must be willing and capable to use adequate contraception during the therapy (all men, all pre-menopausal women). Patients must be able to adhere to the requirements of the Pregnancy Prevention Risk Management Plan. - All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment. - All subjects must agree not to share medication. 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 55 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 56
Exclusion criteria
Exclusion criteria: - Absolute neutrophil count (ANC) 14 mg/dL (> 3.5 mmol/L). - Hemoglobin 3.0 x upper limit of normal (ULN) or serum total bilirubin > 3.0 x ULN) - Prior history of malignancies, other than MM, unless the subject has been free of the disease for = 5 years. Exceptions include the following: Basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, Incidental histological finding of prostate cancer (TNM stage of T1a or T1b). - Previous therapy with pomalidomide or carfilzomib. - Hypersensitivity to thalidomide, lenalidomide, bortezomib or dexamethasone (this includes = Grade 3 rash during prior thalidomide or lenalidomide or bortezomib therapy). - Peripheral neuropathy = Grade 2. - Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant less than 12 months prior to initiation of study treatment - LVEF = 40%. - QTc > 450 msec. - History of torsade de pointe. - History of ventricular tachycardia, ventricular fibrillation. - Uncontrolled atrial fibrillation/flatter. - Congestive heart failure (NY Heart Association Class III or IV). - Myocardial infarction within 12 months prior to starting study treatment - Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris. - History of pulmonary hypertension. - Uncontrolled infection. - Subjects who received any of the following within the last 14 days of initiation of study treatment: Major surgery (kyphoplasty is not considered major surgery), use of any anti-myeloma drug therapy. - Use of any investigational agents (with the exception of lenalidomide) within 28 days or five half-lives (whichever is longer) of treatment. - Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide. - Subjects unable or unwilling to undergo antithrombotic prophylactic treatment. - Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form. - Pregnant or breastfeeding females. - Known human immunodeficiency virus (HIV) positivity, active infectious hepatitis A, B or C or chronic hepatitis B or C. - Pre-existing pulmonary, cardiac or renal impairement that prevents hydration measures as described at section 9.5. - Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Evaluate the efficacy defined as PFS of pomalidomide maintenance plus dexamethasone versus pomalidomide maintenance in patients who responded (= PR) to combination of pomalidomide (POM), carfilzomib (CAR) and low dose dexamethasone (LD-DEX) for induction and consolidation. - Evaluate efficacy of the combination of pomalidomide (POM), carfilzomib (CAR) and low dose dexamethasone (LD-DEX) for induction and consolidation in subjects with relapsed or refractory multiple myeloma (MM) after prior first-line treatment in the EMN02/HO95 trial who are refractory to Lenalidomide and/or Bortezomib. This objective will be investigated in patients who have or have not received a prior autologous transplant. ;Secondary Objective: - Evaluate the response rate after 8 cycles of PCd before the start of maintenance. - Evaluate the safety and tolerability of the combination of pomalidomide, carfilzomib and low dose dexamethasone in subjects with relapsed or refractory multiple myeloma. Exploratory - Evaluation of biomarkers, including baseline markers predictive of response to pomalidomide combined with carfilzomib and dexamethasone. - Evaluate the quality of life - Evaluate the gene expression profiles and SNPs in relation to the treatment outcomes and side-effects ;Primary end point(s): - Progression free survival (PFS) from randomization, defined as time from randomization to progression or death from any cause which ever occur first. Patient still alive at the date of last contact will be censored. - Response rate (sCR, CR, VGPR, PR) after induction and consolidation treatment ;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated when applicable data for all patients are available | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Response rate after 8 cycles of PCD before start of maintenance -Toxicity -Improvement of response during/after maintenance -Progression free survival calculated registration -Overall survival calculated from time of registration or from start of maintenance treatment, until death from any cause. Patients still alive at the date of last contact will be censored. -Quality of life as defined by the EORTC QLQ-C30 and QlQ-MY20. ;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated when applicable data for all patients are available | — |
Countries
Austria, Belgium, Czech Republic, Greece, Italy, Netherlands, Turkey
Contacts
Public ContactHOVON Data Center
HOVON
Outcome results
None listed