Randomized Phase II study of induction isatuximab, bortezomib, lenalidomide, and dexamethasone (I-VRD) followed by autologous stem cell transplantation with or without consolidation I-VRD in patients with transplant-eligible newly diagnosed multiple myeloma (ICON Study)

Not Applicable

Conditions: Neoplasms

Registration Number: KCT0009297

Lead Sponsor: Samsung Medical Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot yet recruiting

Sex: All

Target Recruitment: 188

Inclusion Criteria

1. Newly diagnosed MM as defined by the International Myeloma Working Group criteria (See appendix IA)
2. Age of 18 to 70 years old
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0–2
4. Patient is eligible for high-dose therapy and autologous stem cell transplantation (See appendix 1B)
5. No prior therapy for multiple myeloma other than a short course of corticosteroids
6. Measurable disease meeting at least one of the following criteria (at screening or prior to pre induction):
- Serum monoclonal (M) protein =1.0 g/dl
- = 200 mg of M protein/24h in the urine
- Serum free light chain =10 mg/dL and abnormal kappa to lambda ratio
7. Available FISH report (performed locally or by third party cytogenetics laboratory) that informs absence or presence of high risk chromosome abnormalities [del17p, t(4;14), t(14;16), 1q gain/amplification]
8. Available albumin, beta-2 microglobulin, and lactate dehydrogenase results (at screening or prior to pre induction)
9. Adequate laboratory parameters within 21 days prior to initiation of therapy
- Absolute neutrophil count (ANC) = 1000/mm3 regardless of growth factor support
- Hemoglobin level >7.5 g/dL
- Platelets = 75,000/mm3 independent of transfusion support
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 x upper limit of normal (ULN)
- Total bilirubin < 1.5 mg/dL unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
- Creatinine Clearance = 30 mL/min (determined by using the MDRD formula)
10. Even if HBsAg is positive, if HBV DNA level is < 500 IU/mL and the patient has taken antiviral drugs for more than 2 weeks as of the start of treatment and is willing to follow the antiviral treatment guidelines during the clinical trial, enrollment is possible. If HBsAg is negative but HBcIgG Ab positive, patient can enroll to the trial on the condition that patient will receive prophylactic antiviral treatment
11. Provision of a signed written informed consent
12. Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for = 90 days after the last dose of study drug(s) and must have a negative urine (or serum) pregnancy test = 7 days before initial treatment.
13. Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for = 90 days after the last dose of study drug (a ‘sterile’ male is defined as one for whom azoospermia has been previously demonstrate in a semen sample examination as definitive evidence of infertility)

Exclusion Criteria

1. Diagnosis of amyloidosis, POEMS, Waldenstrom’s macroglobulinemia.
2. Major surgery, radiotherapy or infection requiring therapy within 14 days of starting treatment.
3. History of another primary cancer other than MM, unless the subject has been free of the disease for = 3 years with the exception of the following non-invasive malignancies: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin in situ (stage 0), carcinoma in situ of the cervix, carcinoma in situ of the breast, early gastric cancer, incidental histologic finding of prostate cancer (T1a or T1b) or prostate, cancer that is curative
4. History of allogenic stem cell transplantation (patients with history of autologous stem cell transplantation can be enrolled to the study)
5. Prior history of solid organ transplantation or other cause of severe immunodeficiency
6. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products
7. Unstable angina or myocardial infarction within 4 months prior to registration, NYHA Class III or IV heart failure, 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.
8. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s or Medical Monitor’s judgment, precludes the patient’s safe participation in and completion of the study, or which could affect compliance with the protocol or interpretation of results
9. Cerebrovascular disease manifested as prior stroke at any time or TIA in the 12 months prior to initiation of therapy
10. Known diagnosis of HIV infection (HIV testing is not mandatory). However, HIV+ patients with sustained negative viral load can be enrolled.
11. If hepatitis C antibody result is positive, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before enrollment. Patients who are hepatitis C RNA positive will be excluded.
12. Significant neuropathy (Grades 3–4, or Grade 2 with pain) within 21 days prior to registration
13. Pregnant or lactating females. Lactating females must agree not to breast feed while taking lenalidomide
14. Inability to comply with an anti-thrombotic treatment regimen (e.g., administration of aspirin, enoxaparin, or low molecular weight heparin administration
15. Alcohol or substance abuse disorder