Originele protocol

Pomalidomide combined with Carfilzomib and Dexamethasone (PCd) for induction and consolidation followed by Pomalidomide combined with Dexamethason vs Pomalidomide maintenance for patients with Multiple Myeloma in first relapse after prior 1st line treatment with Lenalidomide and Bortezomib


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.

Exclusion criteria

  • Absolute neutrophil count (ANC) <1.0 x 109/L, unless related to MM.
  • Platelet count < 75 x 109/L, unless related to MM.
  • Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L).
  • Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted).
  • Significant hepatic dysfunction (Serum SGOT/AST or SGPT/ALT > 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.