Smoldering multiple myeloma MedDRA version: 17.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Revlimid 25 mg hard capsules
Product Name: Revlimid
Product Code: CC-5013
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Other descriptive nam
Sponsors
Fundación PETHEMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.-In the investigator's opinion, the patient must be able to fulfill all the clinical trial requirements. 2.-The patient must voluntarily sign the informed consent before any study procedure that is not part of the standard of care for these patients is performed, with the patient's knowledge that he/she may withdraw from the study at any time, without prejudice to his/her future care. 3.-Age older than 18 and younger than 65 years and candidates to receive high-dose therapy and autologous stem cell transplantation. 4.-The patient must be diagnosed with smoldering MM at high risk of progressing to symptomatic MM, or at ultra high risk of progression to symptomatic disease, defined by: - SMM at high risk of progression to symptomatic disease: a. Bone marrow infiltration with plasma cells (PCs) greater than or equal 10% and presence of a monoclonal component, IgG greater than3 g/dL or IgA greater than 2 g/dL or Bence Jones proteinuria greater than 1 g/24h and absence of lytic lesions, hypercalcemia, renal failure (creatinine less than 2 mg/dL) and anemia (hemoglobin greater than 10 gr/dL or not 2 gr/dL below the lower limit of normal). b. Bone marrow infiltration with PCs greater than or equal 10% OR IgG greater than 3 g/dL or IgA greater than 2 g/dL or Bence Jones proteinuria greater than 1g/24h (but not both together) and always in the absence of lytic lesions, hypercalcemia, renal failure and anemia. These patients may be included in the study if they meet the following additional criteria: A percentage of phenotypically aberrant plasma cells (PCs) within the bone marrow (BM) PC compartment (aPC/ BM PC) greater than or equal 95% and immunoparesis, defined as a reduction in the levels of 1 or 2 immunoglobulin (Igs) of more than 25% compared with the normal values of the corresponding Ig. - SMM at ultra high risk of progression to symptomatic disease: a. Presence of more than 1 focal lesion in MRI (ideally whole body MRI). b. Infiltration in the BM equal or higher than 60%. c. Ratio of involved/uninvolved serum FLC higher than 100. 5.-The patient must have an ECOG performance status less than 2. 6.-The patient must be able to attend the scheduled visits. 7.-Women of childbearing potential must have a negative pregnancy test (serum or urine) within the 14 days before the starting the study drug. In addition, sexually active women must agree to use contraceptive methods (hormone contraceptives [oral, injectable or implanted], tubal ligation, intrauterine device, barrier contraceptives with spermicide or have a vasectomised partner) while receiving the study drug. Women of childbearing potential must agree to undergo pregnancy tests every 4 weeks while receiving the study drug (every 14 days for women with irregular menstrual cycles) and 4 weeks after the last dose of study drug. 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 90 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.-Any physical condition or psychiatric disorder that would prevent the patient from signing or understanding the informed consent form. 2.-Previous treatment for smoldering multiple myeloma. 3.-Pregnancy or breastfeeding. 4.-Presence of lytic lesions, anemia, renal failure or hypercalcemia. 5.-Any of the following laboratory abnormalities: -Absolute neutrophil count (ANC) less than 1,000/mm3 -Platelet count less than 75,000/mm3. -Serum GOT or GPT greater than 3 x upper limit of normal -Serum total bilirubin greater than 2 x upper limit of normal 6.-Prior history of neoplasm other than multiple myeloma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the patient has been disease-free for > 5 years. 7.-Major surgery within 4 weeks before inclusion in the study. 8.-Known active infection by human aquired immunodeficiency virus, B or C hepatitis virus. 9.-Any investigational drug within 30 days before inclusion in the study. 10.-Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to enrolment. 11.-Unstable angina or myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker. 12.-Uncontrolled hypertension or uncontrolled diabetes. 13.-Significant neuropathy (Grades 3?4, or Grade 2 with pain) within 14 days prior to enrollment. 14.-Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib). 15.-Contraindication to any of the required concomitant drugs or supportive treatments, including intolerance to hydration due to pre-existing pulmonary or cardiac impairment. 16.-LVEF less than 40 17.-Pulmonary hypertension
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the rate of patients achieving and maintaining immunophenotypic response (Flow-CR) (complete response with minimal residual disease negative by multiparametric flow cytometry) at day +100 after high-dose therapy and autologous stem cell transplantation (HDT-ASCT).;Secondary Objective: 1.-To evaluate the rate of patients achieving and maintaining Flow-CR at 3 and 5 years (complete response with minimal residual disease negative by multiparametric flow cytometry after induction, HDT-ASCT, consolidation and maintenance therapy. 2.-To evaluate the efficacy in terms of conventional responses categories: stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR). 3.-To evaluate the time to progression to symptomatic disease (TTP). 4.-To evaluate the Progression-Free Survival (PFS). 5.-To evaluate the Overall Survival (OS). 6.-To evaluate the safety profile.;Primary end point(s): Immunophenotypic complete remission rate (Flow-CR) at day +100 after induction and HDT-ASCT;Timepoint(s) of evaluation of this end point: Day +100 after induction and HDT-ASCT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.-Immunophenotypic complete remission rate (Flow-CR) after consolidation and at 3 and 5 years after HDT-ASCT. 2.-Response rates (sCR, CR, VGPR and OR) after the different parts of the treatment, induction, HDT-ASCT, consolidation and maintenance. 3.-TTP to symptomatic disease, PFS and OS. 4.-Safety profile of the induction, HDT-ASCT, consolidation and maintenance.;Timepoint(s) of evaluation of this end point: After induction, HDT-ASCT, consolidation and maintenance. And at 3 and 5 years after HDT-ASCT. | — |
Countries
Spain
Contacts
Public ContactÁngel Pérez Romero
Dynamic S.L.
Outcome results
None listed