A Clinical trial to compare the combination of Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone versus the combination of Carfilzomib-Lenalidomide-Dexamethasone in newly diagnosed multiple myeloma patients eligible for autologous stem cell transplantation (IsKia TRIAL)
- Conditions
- newly diagnosed multiple myelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-004844-32-DE
- Lead Sponsor
- European Myeloma Network by EM
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 300
1.Patient with newly diagnosed multiple myeloma and eligible to ASCT, for whom the standard treatment it is not, according to the investigator, the best treatment available.
2.Patient is, in the investigators opinion, willing and able to comply with the study visits and procedures required per protocol.
3.Patient has provided written informed consent in accordance with federal, local, and institutional guidelines prior to initiation of any study-specific activities or procedures. Subject does not have kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
4.Monoclonal plasma cells in the bone marrow b%10% or presence of a biopsy proven plasmacytoma and documented multiple myeloma satisfying at least one of the calcium, renal, anemia, bone (CRAB) criteria or biomarkers of malignancy criteria:
CRAB criteria:
- Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than upper limit of normal (ULN) or >2.75 mmol/L (>11 mg/dL)
- Renal insufficiency: creatinine clearance <40mL/min or serum creatinine >177 N>mol/L (>2 mg/dL)
- Anemia: hemoglobin >2 g/dL below the lower limit of normal or hemoglobin <10 g/dL
- Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT
Biomarkers of Malignancy:
- Clonal bone marrow plasma cell percentage b%60%
- Involved: uninvolved serum FLC ratio b%100
- >1 focal lesion on magnetic resonance imaging (MRI) studies
5.Patient is 18 - 70 years old and is eligible for autologous stem cell transplantation
6.Patient has measurable disease as defined by any one of the following:
- Serum monoclonal paraprotein (M-protein) level b%1.0 g/dL or urine M-protein level b%200 mg/24 hours; or
- Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin FLC b%10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio.
7.Life expectancy b% 3 months
8.ECOG status b$2
9.Clinical laboratory values meeting the following criteria during the Screening Phase:
oAdequate hepatic function, with serum (alanine aminotransferase) ALT b$ 2.5 times the upper limit of normal (ULN), AST (aspartate transaminase) b$ 2.5 x the ULN
oSerum direct bilirubin b$ 1.5 ULN) (except in subjects with congenital bilirubinemia, such as Gilbert syndrome, direct bilirubinemia b$ 1.5 ULN)
oAbsolute neutrophil count (ANC) b% 1.0 109/L
oPlatelet count b% 75 109/L (b% 50 109/L if myeloma involvement in the bone marrow is > 50%) and no platelet infusion in the 1 week prior to screening platelet count
oCreatinine clearance (CrCl) b% 30 mL/minute. Creatinine clearance should be calculated using eGFR (Modified Diet in Renal Disese [MDRD])
oCorrected serum calcium b$ 13.5 mg/dL (3.4 mmol/L)
oLVEF b% 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
10.Females of childbearing potential (FCBP)* complies with the conditions of the Pregnancy Prevention Plan, including confirmation that she has an adequate level of understanding and must agree to ongoing pregnancy testing and to practice contraception or true abstinence. FCBP must use a highly effective and an additional barrier contraception method simultaneously for 4 weeks before starting therapy, during
1.Previous treatment with anti-myeloma therapy (does not include radiotherapy, biphosphonates, or a single short course of steroid b$ to the equivalent of dexamethasone 40 mg/day for 4 days).
2.Patients with non-secretory MM unless serum free light chains are present and the ratio is abnormal or a plasmacytoma with minimum largest diameters of > 2 cm.
3.Patients with plasma cell leukemia, amyloidosis, Waldenstrom Disease, POEMS syndrome
4.Meningeal involvement of multiple myeloma
5.Patient ineligible for autologous transplantation
6.Pregnant or lactating females
7.Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to randomization
8.Known human immunodeficiency virus infection (HIV)
9.Active hepatitis A, B or C infection. Hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response with antiviral therapy are allowed). Tests to be performed if required per local country regulations (in Czech Republic testing for HIV and hepatitis B and C is required at screening). In fact it is not possible to avoid the risk of virological reactivation with the study treatments. Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA
Active HCV infection: positive HCV RNA and negative anti-HCV
10.Unstable angina or myocardial infarction within 4 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, uncontrolled hypertension, (Uncontrolled hypertension, defined as an average systolic blood pressure b% 160 mmHg or diastolic b% 100 mmHg despite optimal treatment (measured following European Society of Hypertension/European Society of Cardiology 2013 guidelines), in the last 5 years pulmonary embolia, 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
11.Non-hematologic or hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
12.Significant neuropathy (Grades 3b4, or Grade 2 with pain) within 14 days prior to randomization as defined by National Cancer Institute Common Toxicity Criteria (NCI CTCAE) 5.0
13.Known history of allergy to CaptisolB. (a cyclodextrin derivative used to solubilize carfilzomib) and to PS80; prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), or known intolerance or hypersensitivity to infused protein products or any of the components (active substance or excipients) of study treatments that are not amenable to premedication with steroids, or H2 blockers, that would prohibit further treatment with these agents.
14.Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoag
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method