A trial for relapsed Multiple Myeloma patients (Isatuximab-dexamethasone)

Prior treatment

• Previous therapy with daratumumab, isatuximab or any other anti-CD38 monoclonal antibody
• Uncontrolled or active HBV infection: patients with positive HBsAg and/or HBV DNA. Of note:
  • 1.1 Subjects can be eligible if: anti-HBc IgG is positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. If anti-HBV therapy in relation with prior infection was started before initiation of study treatment, the anti-HBV therapy and monitoring should continue throughout the study treatment period.
  • 1.2 Subjects with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met.

Lab values

• Active HCV infection: positive HCV RNA and negative anti-HCV. Of note:
  • 2.1 Subjects with antiviral therapy for HCV started before initiation of study treatment and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion.
  • 2.2 Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible.
  • Subject with any concurrent, clinically significant, uncontrolled medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
  • Subject with active tuberculosis and systemic or severe infections requiring treatment with an antibiotic parenteral administration
  • Subject with hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H1 blockers or would prohibit further treatment with these agents
  • Subject with pulmonary deficit, defined as FEV1 <65% and/or DLCO <65%
• Subject with clinically significant cardiac disease, including:
  • 3.1 LVEF <50%
  • 3.2 Myocardial infarction within 6 months before eligibility confirmation, or unstable
  • MM localization to the central nervous system
  • 3.3 Uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV)
  • 3.4 Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] Version 5 Grade 2 or higher) or clinically significant ECG abnormalities
  • 3.5 Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s formula (QTcF) >500 msec
  • Subjects who have received any investigational drug within 14 days or 5 half-lives of the investigational drug from eligibility confirmation, whichever is longer. In case of very aggressive disease, delay could be shortened after agreement between Sponsor and Investigator, in absence of residual toxicities from previous therapy
  • Subjects who have received an allogeneic stem cell transplant
  • Subject with a history of malignancy (other than multiple myeloma) within 3 years before the date of eligibility confirmation (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, in agreement with the medical monitor, is considered cured with minimal risk of recurrence within 3 years)
  • Subject is known to be seropositive for human immunodeficiency virus (HIV) or with an active hepatitis A, B and C infection, defined as a positive test for hepatitis B surface antigen [HBsAg] and a positivity for HAV-RNA, HBV-DNA or HCV-RNA.

• Patient has given voluntary written informed consent
• 1.1 Platelet count ≥50 x 10^9/L (≥30 x 10^9 /L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to drug administration)
• 1.2 Absolute neutrophil count (ANC) ≥ 1 x 10^9/L without the use of growth factors
• 1.3 Corrected serum calcium ≤14 mg/dL (3.5 mmol/L)
• 1.4 Alanine transaminase (ALT): ≤ 3 x the ULN
• 1.5 Total bilirubin: ≤ 2 x the ULN
• 1.6 Calculated or measured creatinine clearance: ≥ 30 mL/minute
• Female subjects are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • 2.1 They are not females of childbearing potential (FCBP)
  • 2.2 They are FCBP who have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days prior to and again within 24 hours of starting study medication and before each cycle of study treatment and must either commit to continue abstinence from heterosexual intercourse or apply a highly effective method of birth control during the intervention period and for at least 5 months after the last dose of study treatment. Of note: contraception duration should take also into consideration any backbone therapy
  • Male subjects must agree to use contraception on this protocol during the intervention period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period
  • Patient is willing and able to comply with the study visits and procedures required per protocol
  • Subject must have at least 18 and ≤ 70 years of age
  • Patient has a life-expectancy ≥ 3 months
  • Subject has received an ASCT in the first line of therapy with a progression/relapse after at least 24 months
  • Subject must have received any cytoreductive treatment, excluding anti-CD38 antibodies containing regimens, as per local practice for the first relapse, according to local guidelines. Carfilzomib-based combinations are recommended (eg. carfilzomib-lenalidomide-dexamethasone or carfilzomib-dexamethasone). After the salvage duration phase (reinduction therapy), subject has achieved at least a PR according to IMWG Response criteria.
  • Subject must have at least 2.0 x 10^6 CD34+/Kg cryopreserved autologous stem cells
  • Subject must have an ECOG Performance Status score of 0, 1
  • 1.Subject must have the following laboratory values: