Overview
Prospective, single center, randomized, open label, parallel group, 2-arm study assessing the clinical benefit in term of enhancement of overall response rate of Isatuximab in combination with CellProtect as compared to Isatuximab for the treatment of patients with newly diagnosed multiple myeloma who are eligible for stem cell transplantation (SCT) as maintenance after SCT.
Eligibility
Inclusion Criteria:
I1. Active multiple myeloma, as defined by the IMWG criteria.
I2. Evidence of measurable disease:
I3. Serum monoclonal (M)-protein ≥1.0 g/dL measured using serum protein
immunoelectrophoresis a.and/or I4. Urine M-protein ≥200 mg/24 hours measured using urine
protein immunoelectrophoresis
a. and/or I5. 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 <0.26 or >1.65.
I6. Patients who are newly diagnosed and considered for high-dose chemotherapy I7. 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withdrawn by the patient at any time without prejudice to his/her medical care.
I8. ≥18 years of age (and satisfying the legal age of consent in the jurisdiction in which
the study is taking place) I9. Eastern Cooperative Oncology Group (ECOG) performance status
score of 0 or 1 I10. Male or Female
1. 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.
2. 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
Screening #2 (Conducted after HDT):
Inclusion criteria as for first screening in addition to response evaluation (at least
partial remission must be met).
Exclusion Criteria:
E1. Prior or concurrent exposure to NK cells and NK like T cells, or Approved or
investigational treatments for MM.
E2. Received any investigational drug within 14 days or 5 half-lives of the investigational
drug, whichever is longer.
E3. 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).
E4. 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.
E5. 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.
E6. Concomitant plasma cell leukemia. E7. 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).
E8. ECOG PS >2. E9. Hemoglobin <8 g/dL. E10. Platelets <70 × 109/L if <50% of bone marrow
(BM) nucleated cells are plasma cells, and ≤30 × 109/L if ≥50% of BM nucleated cells are
plasma cells. Platelet transfusion is not allowed within 3 days before the screening
haematological test.
E11. Total bilirubin >1.5 × upper limit of normal (ULN), except for known Gilbert syndrome.
E12. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 × ULN.
E13. Hypersensitivity (or contraindication) to dexamethasone, 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 that are not amenable to premedication with steroids and H2
blockers or would prohibit further treatment with these agents.
E14. Any of the following within 6 months prior to randomization:
E15. Second/third degree heart block E16. Poorly controlled hypertension E17. Myocardial
infarction E18. Severe/unstable angina pectoris E19. Coronary/peripheral artery bypass
graft E20. New York Heart Association class III or IV congestive heart failure E21. Grade
≥3 arrhythmias E22. Stroke or transient ischemic attack. E23. Left-ventricular ejection
fraction <40%. E24. 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.
E25. 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).