Relapsed/Refractory Multiple Myeloma MedDRA version: 20.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000054086
Conditions
Interventions
Trade Name: Kyprolis
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: CARFILZOMIB
CAS Number: 868540-17-4
Current Sponsor code: CARFILZOMIB
Other descriptive name: CARFILZOMIB
Concentrati
Sponsors
FUNDACIÓN PETHEMA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age = 18 years 2. Performance status (ECOG) =65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: 1. Primary refractory patients defined as not having achieved at least a PR with a prior therapy. 2. Refractoriness to prior proteasome inhibitor therapies, defined as not having achieved at least MR or having progressed under treatment or in the first 60 days after the last dose of the proteasome inhibitor. 3. Non adequate haematological or biochemical parameters as specified below: • Hemoglobin 50%) is present, =50x109/L platelet count is required. • Absolute neutrophil count (ANC) 2.5 x the upper limit range. • Alanine transaminase (ALT): >2.5 x the upper limit range. • Total bilirubin: >2 x the upper limit range. • Calculated or measured creatinine clearance: <30 mL/min (calculated from the Cockcroft and Gault formula) 4. Left ventricular ejection fraction <50%. 5. Absence of recovery from any significant non-haematological toxicity derived from previous treatments. The presence of alopecia and NCI-CTC grade < 2 symptomatic peripheral neuropathy is allowed. 6. Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception). 7. Previous history of any other neoplastic disease in the last five years (except basal cell carcinoma, skin epithelioma or carcinoma in situ of any site). 8. Other relevant diseases or adverse clinical conditions: • Congestive heart failure or angina pectoris, myocardial infarction within 12 months before inclusion in the study. • Uncontrolled arterial hypertension or cardiac arrhythmias (i.e. requiring a change in medication within the last 3 months or a hospital admission within the past 6 months). • History of significant neurological or psychiatric disorders. • Active infection. • Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis). 9. Patient is known to be human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive or to suffer active hepatitis C infection. 10. Concomitant anti-myeloma therapy within 14 days prior to Day 1 of Cycle 1. 11. Limitation of the patient’s ability to comply with the treatment or follow-up protocol. 12. Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of carfilzomib and dexamethasone in combination with cyclophosphamide in terms of progression free survival (PFS) in relapsed/refractory (R/R) multiple myeloma (MM) patients.;Secondary Objective: To evaluate the efficacy in terms of: - Overall response rate (ORR): stringent complete response (sCR) + complete remission (CR) + very good partial response (VGPR) + partial response (PR). - Achievement of immunophenotypic CR - Time to progression (TTP) - Overall survival (OS). To evaluate the safety determined by the incidence of clinical and analytical toxicities. To evaluate the influence of subclones and biomarkers on the sensitivity and resistance to carfilzomib in combination with dexamethasone either with or without cyclophosphamide.;Primary end point(s): Progression Free Survival (PFS) to carfilzomib + dexamethasone + cyclophosphamide;Timepoint(s) of evaluation of this end point: Progression Free Survival (PFS) is defined as the number of months from randomization to the earlier of disease progression or death due to any cause. Disease outcome determined will be the primary data source for the final PFS analysis. The primary analysis of PFS (and other efficacy endpoints unless specified otherwise) will include all randomized patients that received at least one dose of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The analysis of the secondary efficacy endpoints Overall Rate Response, TIme to Progression and Overall Survival will be based on all randomized patients that received at least one dose of study treatment;Secondary end point(s): - Overall Rate Response (ORR), rate of inmmunophenotypic Complete Response (CRi), TIme to Progression (TTP) and Overall Survival (OS). - The grade and frequency of clinical and laboratory toxicities (AE/SAEs), and treatment discontinuations. - Evaluation of the influence of the subclonal heterogenicity and biomarkers on the sensittivity/resistance of carfilzomib. | — |
Countries
Spain
Contacts
Public ContactJuan José Lahuerta Palacios
FUNDACIÓN PETHEMA
Outcome results
None listed