Isa-RVD Study in Patients With Newly Diagnosed Multiple Myeloma

Inclusion Criteria:

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

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performance of any study-relatedprocedures not part of normal medical care, with the understanding that consent maybe withdrawn by the patient at any time without prejudice to their future medicalcare.

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 serumFLC 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 14days before first study treatment administration)

• Platelet count ≥75,000 cells/dL (75 x 10^9/L) if <50% BM nucleated cells areplasma cells, ≥30,000 cells/dL (30 x 10^9/L) if ≥50% of BM nucleated cells areplasma cells (without transfusions required during the 3 days prior to thescreening haematologic test)

• Total bilirubin ≤2.0 X ULN (except patients with Gilbert Syndrome, who areeligible 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 forLenalidomide and be willing and able to comply with the requirements of thisprogramme.

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

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

Exclusion Criteria:

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

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

3. Central nervous system involvement.

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

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

6. Concurrent uncontrolled cardiovascular conditions, including uncontrolledhypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heartfailure, unstable angina, Grade 3 thromboembolic event or myocardial infarctionwithin 6 months prior to enrolment.

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

8. Daily requirement for corticosteroids (equivalent to >10 mg/day prednisone for morethan 7 days (except for inhalation corticosteroids). Patients may receivecorticosteroids for the management of their MM that should not exceed the equivalentof 160mg of dexamethasone in a 2-week period and should be stable for at least 7days 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 theparticipation in the study. FCBP unwilling to prevent pregnancy by the use of ahighly effective method of contraception for ≥4 weeks before the start of studytreatment, during treatment (including dose interruptions), and up to 5 monthsfollowing the last dose of study treatment and/or who are unwilling or unable to betested for pregnancy before study treatment initiation (2 negative tests), weeklyduring first month of treatment and then prior each treatment cycle administrationor every 2 weeks in case or irregular menstrual cycles up to 5 months following thelast dose of study treatment.

14. Male participants who disagree to practice true abstinence or disagree to use highlyeffective contraception during sexual contact with a pregnant female or FCBP whileparticipating in the study during dose interruptions and at least 5 months followingstudy 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) hasnot undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturallypostmenopausal (amenorrhea following cancer therapy does not rule out childbearingpotential) for at least 24 consecutive months (i.e. has had menses at any time inthe preceding 24 consecutive months). Note 2: True abstinence is acceptable whenthis is in line with the preferred and usual lifestyle of the patient. Periodicabstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) andwithdrawal are not acceptable methods of contraception.

15. Receiving any other investigational agents.

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

17. Inability to tolerate thromboprophylaxis.

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