Multiple myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Velcade 3.5mg
Product Name: Velcade
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Concentration unit: mg milligram(s)
Sponsors
Fundación PETHEMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Newly diagnosed multiple myeloma patients who require start active treatment according to the IMWG published in 2014 [5] 2. Age between 65 and 80 years, both included 3. Fit patient assessed using the comprehensive health status assessment scale (Geriatric Assessment in Hematology, GAH scale, annex 11) (0-94 points GAH scale) [2]. Patients with a punctuation =42 will be included. 4. Signed informed consent 5. Patients must have measurable disease 6. Measurable disease, defined as follows: a. For secretory Multiple Myeloma, measurable disease is defined as the presence of quantifiable monoclonal component, = 0.5 g/dL or, the urine light chains excretion is 200 mg/24h or higher. b. For oligosecretory or non secretory Multiple Myeloma, the level of the affected serum free light chain must be = 10 mg/dL (= 100 mg/L, with an abnormal free light-chain ratio) 7. Eastern Cooperative Oncology Group (ECOG) Performance status =2 (see annex 6). 8. Life expectancy more than 3 months 9. Adequate organ functions: a. Platelet count = 50000/mm3, hemoglobin = 8 g/dl and absolute neutrophil count = 1000/mm3. Lower values are allowed only if they are due to BM infiltration. b. Aspartate Transaminase (AST) and Alanine Transaminase (ALT) = 2.5 x Upper Limit of Normal. c. Total bilirubin: =2 x Upper Limit of Normal. d. Serum creatinine = 2 mg/dl. e. Calcium =14mg/dl or corrected serum calcium =14mg/dl in patients whose albumin level is out of range (see annex 9). 10. Left ventricle ejection fraction = 40% 11. At the discretion of the investigator patient must be able to adhere to all study requirements. 12. .Male patients that receives lenalidomide should commit to use of a condom while taking the study drug every time he has sexual contact with a pregnant female of female of childbearing potential even if he has undergone a successful vasectomy; or practice complete abstinence (when this is the preferred and usual lifestyle of the subject); including during periods of dose interruptions and for at least 30 days after treatment completion. Also males under lenalidomide should commit not to donate semen or sperm during study drug treatment, including during periods of dose interruptions, and for at least 90 days after treatment completion. NOTE: Given the age of patients to be included on this Clinical Trial (between 65 and 80 years, both included), there is no possibility of Females of Childbearing Potential (FCBP), therefore the Pregnancy Prevention Program (annex 12) has been modified accordingly. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 462
Exclusion criteria
Exclusion criteria: 1. Patients older than 81 years or younger than 65 2. Patients that do not qualify for fit according to the GAH scale (annex 11) (>43 points GAH scale) 3. Non adequate organ functions a. Platelet count 2.5 x Upper Limit of Normal. c. Total bilirubin: >2 x Upper Limit of Normal. d. Serum creatinine > 2 mg/dl. e. Calcium >14mg/dl or corrected serum calcium >14mg/dl in patients whose albumin level is out of range (see annex 9). 4. Patients who have previously received treatment for multiple myeloma, except for steroid pulses in case of emergency, the administration of bisphosphonates or antialgic radiotherapy or due to the presence of plasmacytomas requiring some emergency. 5. Men who does not agree to use a condom every time he has sexual contact with a pregnant female or female of childbearing potential, even if he has undergone a successful vasectomy, or men who does not agree to practice complete abstinence (if this is the preferred and usual lifestyle of the subject). 6. Left ventricular ejection fraction <40%. 7. Prior history of malignancies, other than multiple myeloma (except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or the breast), unless the patient has been free of the disease for = 5 years. 8. Other relevant diseases or adverse clinical conditions: a. Myocardial infarction within the 6 months prior to inclusion in the clinical trial b. A NYHA functional class III-IV, heart failure, uncontrolled angina, uncontrolled ventricular arrhythmia or acute ischemia detected electrocardiographically or conduction system anomalies. c. History of significant neurological or psychiatric disorders. d. Active infection. e. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis). f. Poorly controlled arterial hypertension. g. Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form. 9. Human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive or active hepatitis C infection 10. Limitation of the patient’s ability to comply with the treatment or follow-up protocol. 11. Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months). 12. Patients having a peripheral neuropathy = Grade 2 within the 14 days prior to inclusion. 13. Known hypersensibility to any of the study drugs or their excipients. 14. Patients treated with any investigational drug during the previous 30 days. 15. Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease. 16. Patients who are unable or unwilling to undergo antithrombotic therapy. 17. Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy, in terms of immunophenotypic complete responses at 18 months, of the standard treatment in Spain for newly diagnosed multiple myeloma patients not candidates to stem cell transplantation, VMP followed by Rd, with the experimental scheme KRd (carfilzomib, lenalidomide and dexamethasone) (used either alone or in combination with daratumumab) as induction treatment during 18 cycles in a selected fit population of patients with newly diagnosed multiple myeloma.;Secondary Objective: 1.To compare the PFS. PFS2, TTP, OS and response will also be compared. 2.To correlate the kinetics of MRD clearance with PFS in order to assess which time point represents the optimal surrogate marker for PFS. 3.Based on MRD assessment by next generation flow: a To compare the efficacy of VMP with the experimental alkylator-free combination KRd (plus/minus dara). b To investigate the capacity of consolidation with dara-lena to reduce MRD levels in patients treated in the control arm as well as those that received KRd without dara. In addition we will explore if this short consolidation can abrogate the potential benefit of a prolonged induction with KRd+dara. c To investigate the capacity of maintenance therapy to preserve the response obtained both in MRD negative and MRD positive patients. 4.To correlate immunophenotypic response to conventional response and classical survival endpoints. 5.To assess QoL evolution 6.To assess safety for every treatment arm and phase.;Primary end point(s): Difference between each experimental arm and the control group in the proportion of immunophenotypic complete response (flow-MRD negativity);Timepoint(s) of evaluation of this end point: After 18 cycles of induction treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS, PFS2, TTP, OS probabilities and in proportions of conventional response (sCR, CR, VGPR and PR) between each experimental arm and the control group. 2. Kinetics of MRD clearance 3. MRD assessment by next generation flow. 4. Correlation of classical efficacy/survival endpoints with immunophenotypic response: 4.a Conventional responses categories: sCR, CR, VGPR and PR. 4.c Time from randomization to first disease progression or to the moment in which the second line of therapy starts: PFS2. 4.d Overall survival 5. Difference in quality of life scores through EQ-5D/5L, QLQ-C30 and MY20 questionnaires. 6. Counts and proportions of treatment related adverse events for every treatment arm and treatment phase.;Timepoint(s) of evaluation of this end point: - Induction: cycles 9 and 18 - Post-consolidation - Annually during maintenance treatment - QoL: Induction: cycles 6, 12 and 18, post-consolidation and every 6 months during maintenance | — |
Countries
Spain
Contacts
Public ContactMamen Jiménez Aranda
Dynamic S.L.
Outcome results
None listed