Isatuximab for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- Active multiple myeloma, as defined by the IMWG criteria\n- Male of female: 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)\n- Screening #2 (Conducted after HDT): Inclusion criteria I7-I10 in addition to response evaluation (at least partial remission must be met)\n- Evidence of measurable disease: Serum monoclonal (M)-protein ≥1.0 g/dL measured using serum protein immunoelectrophoresis a.\tand/or\n- Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis a.\tand/or\n- 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.\n- Patients who are newly diagnosed and considered for high-dose chemotherapy\n- 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performance of any study related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his/her medical care.\n- ≥18 years of age (and satisfying the legal age of consent in the jurisdiction in which the study is taking place)\n- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2\n- Male or Female: Male participants a. A male participant must agree to use contraception specified in 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"}

Exclusion criteria

• {"criterion_text":"- Prior or concurrent exposure to NK cells and NK like T cells, or Approved or investigational treatments for MM\n- 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\n- Total bilirubin >1.5 × upper limit of normal (ULN), except for known Gilbert syndrome\n- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >3 × ULN\n- 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\n- Second/third degree heart block within 6 months prior to randomization\n- Poorly controlled hypertension within 6 months prior to randomization\n- Myocardial infarction within 6 months prior to randomization\n- Severe/unstable angina pectoris within 6 months prior to randomization\n- Coronary/peripheral artery bypass graft within 6 months prior to randomization\n- Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer\n- Grade ≥3 arrhythmias within 6 months prior to randomization\n- Stroke or transient ischemic attack within 6 months prior to randomization\n- Left-ventricular ejection fraction <40% within 6 months prior to randomization\n- 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\n- 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)\n- 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)\n- 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\n- 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\n- Concomitant plasma cell leukemia\n- 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)\n- ECOG PS >2\n- Hemoglobin <8 g/dL"}

Primary endpoints

• {"endpoint_text":"- Enhancement of ORR (yes/no), defined as “yes” for patients that show an increase in ORR at Visit 15 (start of cycle 4) as compared to Visit 2 (baseline), and “no” otherwise.","definition_or_measurement_approach":"Defined as “yes” for patients that show an increase in ORR at Visit 15 (start of cycle 4) compared to Visit 2 (baseline); measured by comparison of ORR at those visits."}

Secondary endpoints

• {"endpoint_text":"- Overall Response Rate (ORR, scores 1-7) defined as the highest class fulfilled by the patient at one time point: 1. PD, 2. SD or MR (SD, not fulfilling PD, MR, PR, VGPR or CR, or Minimal Response, ≥ 25% reduction in serum M-protein), 3.PR ≥ 50% reduction in serum M-protein, 4. VGPR ≥ 90% reduction in serum M-protein, 5.\tCR (Serum immunofixation not measurable), 6. Flow MRD negative, 7. Sustained MRD negative (compared to Visit 2)","definition_or_measurement_approach":"ORR scored 1-7 as defined in endpoint text; highest class fulfilled at a time point compared to baseline (Visit 2)."}
• {"endpoint_text":"- Treatment-emergent adverse events/serious adverse events (TEAEs/SAEs) (including IARs)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Laboratory parameters","definition_or_measurement_approach":""}
• {"endpoint_text":"- Vital signs","definition_or_measurement_approach":""}
• {"endpoint_text":"- Weight","definition_or_measurement_approach":""}
• {"endpoint_text":"- ECOG PS","definition_or_measurement_approach":""}
• {"endpoint_text":"- Findings from physical examination","definition_or_measurement_approach":""}

Sweden

Earliest CTIS Part Ii Submission Date

26-08-2024

Latest Decision Or Authorization Date

26-09-2024

Processing Time Days

31

Number Of Sites

1

Number Of Participants

62

Primary sponsor

Full Name

Karolinska Institutet

Organisation Type

Educational Institution

Country Of Registered Address

Sweden