Multicenter Open label Phase 3 study of Isatuximab plus Lenalidomide and Dexamethasone with/without Bortezomib in the Treatment of Newly diagnosed Non Frail transplant Ineligible Multiple Myeloma elderly patients (= 65; < 80 years).
- Conditions
- MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-004602-59-FR
- Lead Sponsor
- CHU DE POITIERS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 270
1.Life expectancy > 6 months
2.Subject, male or female, must be at least = 65 years of age and < 80 years of age
3.Must have a Newly diagnosed Multiple Myeloma requiring therapy (SLiM CRAB criteria)
3.1-Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven plasmacytoma
3.2-Revised International Myeloma Working Group diagnostic criteria for multiple myeloma
Myeloma defining events:
oEvidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
• Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)
• Renal insufficiency: creatinine clearance =40 mL per min† or serum creatinine =177 µmol/L (=2 mg/dL)
o Anemia: hemoglobin value of = 20 g/L below the lower limit of normal, or hemoglobin value =100 g/L
o Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT
o Any one or more of the following biomarkers of malignancy:Clonal bone marrow plasma cell percentage =60%/Involved/uninvolved serum free light chain ratio =100
•>1 focal lesion on MRI studies (Each focal lesion must be 5 mm or more in size.)
4.Must have measurable disease as defined by any of the following: IgG myeloma: Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M- protein level =200 mg/24 hours;or IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level =0.5 g/dL or urine M- protein level =200 mg/24 hours;or Light chain multiple myeloma: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
5.Must be NTE Non Frail
5.1.Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT.
5.2.Subject must have a Frailty Score < 2
6.Eastern Cooperative Oncology Group performance status score of 0, 1, or 2
7.Adequate bone marrow function, documented within 72 hours and without transfusion 72 hours prior to the first intake of investigational product (C1J1) with no growth factor support (one week), defined as: -Absolute neutrophils = 1 x109/L, -Untransfused Platelet count = 75 x109/L-Hemoglobine =8.5 g/L
8.Adequate organ function defined as:-Serum total bilirubin < 2.0 mg/dL-Creatinine clearance = 30ml/min-Serum SGOT/AST or SGPT/ALT < 3x upper limit of normal
9.A man who is sexually active with a pregnant woman or a woman of childbearing potential must agree to use a barrier method of birth control e.g., condom with spermicidal foam/gel/film/cream/suppository during the study and for at least 5 months after the last dose of treatment, even he has had a vasectomy. All men must also not donate sperm, spermatozoa during the study, for 5 months following treatment discontinuation.
10.A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
10.1.Not a female of childbearing potential Or 10.2.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 prior to starting study medication and before each cycle of study treatment.
10.2.1.For at least 28 days before starting experimental treatments, 10.2.2.Throughout the entire duration of experimentaltreatments, 10.2.3.During dose interruptions, 10.2.4.And for at least 5 months after the last dose of experimental treatments.
11.All patients must agree to not donate blood du
1.Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage .
2.Subject has a diagnosis of Waldenstro¨m’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
3.Subject has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment
4.Subject has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years).
5.Subject has had radiation therapy and plasmapheresis within 7 days of randomization
6.Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
7.known to be seropositive for history of HIV or to have hepatitis A active infection.
8.Known to have hepatitis B active or uncontrolled infection (positive HBsAg and/or HBV DNA)
9.Known to have hepatitis C active infection (positive HCV RNA and negative anti-HCV)
10.Subject has any clinically significant medical or psychiatric condition or disease (e.g., uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) in the investigator’s opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results.
11.Subject has active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics.
12.Subject has clinically significant cardiac disease, including: myocardial infarction within 6 months before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function and uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
13.Subject has known allergies, hypersensitivity, or intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl ,fumarate, histidine base , arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents, monoclonal antibodies or human proteins, or their excipients
14.Known hypersensitivity, allergy to one of the study product or to one of the excipients.
15.Acute diffuse infiltrative pneumopathy, pericardial disease
16..Subject has plasma cell leukemia criterion: =20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 × 109/L) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
17.Subject is known or suspected of not being able to comply with the study protocol (e.g., because
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method