Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: CellProtect
Pharmaceutical Form: Infusion
Trade Name: Sarclisa
Product Name: Isatuximab
Pharmaceutical Form: Infusion
INN or Proposed INN: ISATUXIMAB
CAS Number: 1461640-62
Concentratio
Sponsors
Karolinska Institutet
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Active multiple myeloma, as defined by the IMWG criteria. 2. Evidence of measurable disease: 3. Serum monoclonal (M)-protein =1.0 g/dL measured using serum protein immunoelectrophoresis a. and/or 4. Urine M-protein =200 mg/24 hours measured using urine protein immunoelectrophoresis a. and/or 5. in patients without measurable M protein in serum or urine as per previous criteria, serum immunoglobulin free light chain (sFLC) =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio 1.65. 6. Patients who are newly diagnosed and considered for high-dose chemotherapy 7. Patient has given 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performance of any study related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his/her medical care. 8. =18 years of age (and satisfying the legal age of consent in the jurisdiction in which the study is taking place) 9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 10. Male or Female a) Male participants A male participant must agree to use contraception of 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. b) Female participants A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a Females of childbearing potential (FCBP), OR A FCBP who must 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 must either commit to continue abstinence from heterosexual intercourse or apply a highly effective method of birth control until at least 5 months after last dose of study treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Prior or concurrent exposure to NK cells and NK like T cells, or Approved or investigational treatments for MM. 2. Diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage). 3. Diagnosis of Waldenström's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions. 4. Prior or current systemic therapy, or SCT for symptomatic multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids, if completed within 14 days prior to randomization. 5. Concomitant plasma cell leukemia. 6. Any major procedure within 14 days before the initiation of the study treatment: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy (except if palliative intent). 7. ECOG PS >2. 8. Hemoglobin 1.5 × upper limit of normal (ULN), except for known Gilbert syndrome. 11. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 × ULN. 12. Hypersensitivity (or contraindication) to steroids, sucrose histidine (as base and hydrochloride salt), boron, mannitol, and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids, pregelatinized starch, sodium stearyl fumarate, arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy 13. Any of the following within 6 months prior to randomization: 14. Second/third degree heart block 15. Poorly controlled hypertension 16. Myocardial infarction 17. Severe/unstable angina pectoris 18. Coronary/peripheral artery bypass graft 19. New York Heart Association class III or IV congestive heart failure 20. Grade =3 arrhythmias 21. Stroke or transient ischemic attack. 22. Left-ventricular ejection fraction <40%. 23. Prior malignancy. Adequately treated basal cell or squamous cell skin, or superficial (pTis, pTa, and pT1) bladder cancer, or low risk prostate cancer, or any in situ malignancy after curative therapy are allowed, as well as any other cancer for which cytotoxic chemotherapy has been completed =3 years prior to enrolment and from which the patient has been disease-free for =3 years. 24. Known acquired immunodeficiency syndrome (AIDS)-related illness or known HIV disease requiring antiviral treatment or active hepatitis A (defined as positive HA antigen), B (defined as either positive HBs antigen or negative HBs antigen with positive HBc antibody), or C infection (defined as a known positive hepatitis C antibody result and known quantitative hepatitis C (HCV) ribonucleic acid (RNA) results greater than the lower limits of detection of the assay).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the benefit of Isatuximab (ISA) in combination with CellProtect in the enhancement of overall response rate (ORR) as compared to Isatuximab in patients with newly diagnosed multiple myeloma (NDMM) eligible for transplant as maintenance treatment after high dose treatment (HDT).;Secondary Objective: To evaluate the time to progression (TTP). To evaluate PFS. To evaluate the duration of response (DOR). To evaluate the overall survival (OS). To evaluate safety. Exploratory objectives: To evaluate comparative serum cytokine and chemokine profiling in both arms To evaluate comparative detailed phenotypic analyses of BMMC and PBMCs in both arms To evaluate the CD38 expression of circulating activated NK cells;Primary end point(s): To evaluate in both randomized (ISA and ISA/CellProtect) arms the occurrence after maintenance start of: Very good partial response (VGPR) or better rate, as defined by the International Myeloma Working Group (IMWG) criteria. Co-primary objective will be assessment of minimal residual disease (MRD) negativity rate in patients with CR or VGPR and conversion from MRD positive to MRD negative checked after first cycle of Isatuximab and before start of monthly Isatuximab. The aforementioned assessment will also be conducted at 12 and 24 months after start maintenance. Complete response (CR) rate, as defined by the IMWG criteria. MRD negativity rate for both CR and VGPR patients, defined as the proportion of patients for whom MRD is negative. Bone marrow aspirates will be collected. Threshold for negativity will be at least 10-5. ;Timepoint(s) of evaluation of this end point: Continously from start of study treatment until end of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Progression-free survival on/after study medication, defined as the time from the date of the start of maintenance treatment to the date of documented progressive disease (PD) or death, whichever comes first. • Time from the date of randomization to the date of initial documented progression according to the International Myeloma Working Group (IMWG) diagnostic criteria for MM requiring systemic therapy or to the date of death, whichever occurs first. • TTP, defined as the time from randomization to the date of first documentation of PD (as determined by the IRC using the IMWG criteria). • DOR, defined as the time from the date of the first IRC determined response to the date of first IRC PD or death, whichever occurs first. Duration of response will determined only for patients who have achieved CR, VGPR, or PR. • PFS (defined as the time from the date of randomization to the date of first documentation of PD or the date of death from any cause, whichever comes first by MRD status. • OS, defined as the time from the date of randomization to death from any cause. Safety in terms of treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) (including IARs), laboratory parameters, vital signs, weight, ECOG PS, and findings from physical examination. TEAEs are defined as AEs that develop, worsen (according to the Investigator opinion), or become serious during the treatment period. The treatment period is defined as the time from first dose of study treatments up to 30 days after last dose of study treatments or initiation of further anti-myeloma therapy, whichever occurs first. ;Timepoint(s) of evaluation of this end point: Continously until end of study | — |
Countries
Sweden
Contacts
Public ContactDepartment of Medicine, Hematology
Karolinska Institutet
Outcome results
None listed