A RANDOMIZED TRIAL THAT COMPARE CARFILZOMIB - LENALIDOMIDE - DEXAMETHASONE versus LENALIDOMIDE - DEXAMETHASONE IN NEWLY DIAGNOSED MYELOMA PATIENTS NOT ELIGIBLE FOR AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT)

Phase 1

• Conditions: PATIENTS WITH NEW DIAGNOSIS MM WITH AGE = 65 YEARS OR NOT ELIGIBLE TO ASCT; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-002068-15-IT
• Lead Sponsor: FO.NE.SA.Onlus

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-02-14
• Last Update Posted: 7 September 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 340

Inclusion Criteria

•Newly diagnosed symptomatic MM based on either standard CRAB criteria (at least 10% of clonal bone marrow plasma cells plus CRAB defined as the onset of any of the following clinical symptoms: hypercalcemia, renal failure, anemia and bone lesions) or at least 10% of bone marrow plasma cells plus the presence of at least one of the following biomarkers of malignancy:
?60% or greater clonal plasma cells on bone marrow examination;
?Serum involved/uninvolved free light chain (FLC) ratio of 100 or greater;
?More than one focal lesion on magnetic resonance imaging (MRI) that is at least 5 mm or greater in size.
•Patient not eligible for ASCT (age = 65 years or abnormal cardiac, pulmonary and liver function).
•Patient defined as fit or intermediate according to the IMWG (International Myeloma Working Group) frailty score
•Patient has given voluntary written informed consent.
•Patient agrees to use acceptable methods for contraception.
•Patient has measurable disease according to IMWG criteria.
•Patient has ECOG (Eastern Cooperative Oncology Group) performance status < 3.
•Pre-treatment clinical laboratory values within 30 days before randomization:
•Platelet count =50 x 109/L (=30 x 109 /L if myeloma involvement in the bone marrow is > 50%)
•Absolute neutrophil count (ANC) = 1 x 109/L without the use of growth factors
•Corrected serum calcium =14 mg/dL (3.5 mmol/L)
•Alanine transaminase (ALT): = 3 x the ULN
•Total bilirubin: = 2 x the ULN
•Calculated or measured creatinine clearance: = 30 mL/minute.
•LVEF= 40%: 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation; multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available
•Pre-treatment blood pressure value < 140/90 mmHg even with adequate therapy: 24 hours blood pressure monitoring is the preferred method of evaluation; blood pressure diary at home for 2 weeks is acceptable.
•Females of childbearing potential (FBCP) must follow the Pregnancy Prevention Plan and use a highly effective and an additional barrier contraception method simultaneously for 4 weeks before starting therapy, during treatment and dose interruptions and for at least 30 days after the last dose of study drugs*
•Males must use an effective barrier method of contraception if sexually active with FCBP during the treatment and for at least 90 days after the last administration of study drug/s. Male subjects must agree to refrain from sperm donation for at least 90 days after the last dose of carfilzomib.
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 340

Exclusion Criteria

•Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the screening or place the subject at unacceptable risk.
•Patient defined as frail according to the IMWG frailty score
•Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid < to the equivalent of dexamethasone 40 mg/day for 4 days)
•Pregnant or lactating females
•Presence of:
•Clinical active infectious hepatitis type A, B, C or HIV
•Acute active infection requiring antibiotics or infiltrative pulmonary disease
•Pulmonary hypertension and interstitial lung disease
•Uncontrolled arrhythmias or history of QT prolongation
•Myocardial infarction or unstable angina = 6 months or other clinically significant heart disease
•Peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 5.0 (Appendix A)
•Uncontrolled hypertension defined as persistent hypertension (>140/90 mmHg) regardless treatment with 3 drugs, including a diuretic.
•Contraindication to any of the required drugs or supportive treatments
•Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
•Invasive malignancy within the past 3 years

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified