Isa-RVD Study in Patients With Newly Diagnosed Multiple Myeloma

Isa-RVD Study: Phase II, Multi-centre, Single-Arm, Open-Label Study to Evaluate the Efficacy and Safety of the Combination Regimen Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma

This study aims to evaluate the stringent Complete Response (sCR) rate by the end of two cycles of induction treatment, defined as the proportion of patients who have achieved sCR, according to International Myeloma Working Group (IMWG) criteria, by the end of two cycles of induction treatment.

Inclusion Criteria:

1. Previously diagnosed with MM based on standard IMWG criteria and currently requires treatment.

2. Provided voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.

3. Age ≥18 years, ≤75 years, with patients over the age of 70 requiring CI approval.

4. Measurable disease defined as at least one of the following:

   • Serum M protein ≥0.5g/dL (≥5g/L)
   • Urine M protein ≥200 mg/24 hours
   • Serum FLC assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).

5. Screening laboratory evaluations within the following parameters:

   • ANC ≥ 1,000 cells/dL (1.0 x 10^9/L) (growth factors cannot be used within 14 days before first study treatment administration)
   • Platelet count ≥75,000 cells/dL (75 x 10^9/L) if <50% BM nucleated cells are plasma cells, ≥30,000 cells/dL (30 x 10^9/L) if ≥50% of BM nucleated cells are plasma cells (without transfusions required during the 3 days prior to the screening haematologic test)
   • Total bilirubin ≤2.0 X ULN (except patients with Gilbert Syndrome, who are eligible if total bilirubin <3.0 mg/dL)
   • AST (SGOT) and ALT (SGPT) ≤3.0 x ULN
   • Haemoglobin ≥8g/dL
   • Calculated CrCl ≥30 mL/min

6. ECOG performance status ≤ 2 (Appendix B).

7. Participant agrees to be registered into the mandatory Risk Management Programme for Lenalidomide and be willing and able to comply with the requirements of this programme.

8. Ability to understand and the willingness to sign a written informed consent document.

9. Participant is considered eligible for ASCT by the treating physician.

Exclusion Criteria:

1. Prior therapy for MM. Participants who received smouldering treatment qualify to participate as long as the prior treatment was not a CD38 therapy.

2. Diagnosed or treated for another malignancy within 3 years prior to enrolment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy.

3. Central nervous system involvement.

4. Peripheral neuropathy ≥ Grade 3, or Grade 2 with pain on clinical examination during the screening period.

5. Any medical or psychiatric illness that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study.

6. Concurrent uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, Grade 3 thromboembolic event or myocardial infarction within 6 months prior to enrolment.

7. Prior major surgical procedure or radiation therapy within 4 weeks of initiation of study treatment (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of study treatment)

8. Daily requirement for corticosteroids (equivalent to >10 mg/day prednisone for more than 7 days (except for inhalation corticosteroids). Patients may receive corticosteroids for the management of their MM that should not exceed the equivalent of 160mg of dexamethasone in a 2-week period and should be stable for at least 7 days prior to the initiation of study treatment.

9. Concurrent symptomatic amyloidosis or plasma cell leukaemia.

10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).

11. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of start of study treatment.

12. Active hepatitis B or hepatitis C viral infection.

13. Pregnant or breastfeeding female or female who intends to become pregnant during the participation in the study. FCBP unwilling to prevent pregnancy by the use of a highly effective method of contraception for ≥4 weeks before the start of study treatment, during treatment (including dose interruptions), and up to 5 months following the last dose of study treatment and/or who are unwilling or unable to be tested for pregnancy before study treatment initiation (2 negative tests), weekly during first month of treatment and then prior each treatment cycle administration or every 2 weeks in case or irregular menstrual cycles up to 5 months following the last dose of study treatment.

14. Male participants who disagree to practice true abstinence or disagree to use highly effective contraception during sexual contact with a pregnant female or FCBP while participating in the study during dose interruptions and at least 5 months following study treatment discontinuation, even if he has undergone a successful vasectomy.

    Note 1: a FCBP is a female who: 1) has achieved menarche at some time point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e. has had menses at any time in the preceding 24 consecutive months). Note 2: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

15. Receiving any other investigational agents.

16. Hypersensitivity to steroids, or H2 blockers that would prohibit further treatment with these agents.

17. Inability to tolerate thromboprophylaxis.

18. Hypersensitivity (or contraindication) to dexamethasone, sucrose histidine (as base and hydrochloride salt), boron, mannitol, and polysorbate 80, or to any of the components of the study therapy.