Multicenter Open label Phase 2 study of Isatuximab plus Pomalidomide and Dexamethasone with Carfilzomib in Relapsed or Refractory Multiple Myeloma
- Conditions
- MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-001027-12-FR
- Lead Sponsor
- CHU de Poitiers
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
- Male or female, age 18 years or older
- Life expectancy of > 6 months.
- Must be in R1 (Line 2) and R2 (Line 3) relapse Multiple Myeloma with a measurable disease
o Have had 1 to maximum 2 lines of therapy prior to study entry
o Relapse Refractory or primary refractory or relapse
o Must have received prior treatment with a Lenalidomide-containing regimen for at least 2 consecutive cycles
- Must have measurable disease as defined by the following: must have a clearly detectable and quantifiable monoclonal M-component value in the serum and/or urine.
o IgG/IgA (serum M-component > 5g/l),
o Light chain (serum M-component >1g/l or Bence Jones > 200mg/24H),
o Serum FLC assay (including for IgD isotypes): involved FLC level > 10 mg/dl provided serum.
FLC ratio is abnormal for patients not measurable on any of the 3 above criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
- Wash out period without MM treatment must be of 28 days minimum before C1D1, except for anti CD-38
- 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:
o Absolute neutrophils = 1 x109/L,
o Untransfused Platelet count = 75 x109/L,
o Hemoglobine = 8.5 g/dL.
-Adequate organ function defined as:
o Serum total bilirubin < 2.0 mg/dL,
o Clairance creatinine = 30ml/min,
o Serum SGOT/AST or SGPT/ALT < 3x upper limit of normal (ULN).
- Patients affiliated to an appropriate social security system.
- A man who is sexually active with a pregnant female or a FCBP* must agree to use a barrier method of birth control eg, condom with spermicidal foam/gel/film/cream/suppository, even if he has had a vasectomy. All men must also not donate sperm, spermatozoa during the study, for 19 weeks following treatment discontinuation.
- A woman FCBP* must understand and agree to use 2 reliable effective methods (a very effective method and an effective additional method) of contraception simultaneously without interruption:
o For at least 28 days before starting experimental treatments
o Throughout the entire duration of experimental treatments,
o During dose interruptions,
o And for at least 19 weeks after the last dose of experimental treatments.
- All patients must agree to not donate blood during the treatment period, interruptions of treatment and at least 19 weeks after the last dose of treatment
- All patients must understand and accept to comply with the conditions of the Pomalidomide pregnancy prevention plan
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 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80
- Any other uncontrolled medical condition or comorbidity that might interfere with subject’s participation.
- Known positive for HIV or active infectious hepatitis, type B or C.
- Patients with non-secretory MM and non-measurable MM
- Patient with terminal renal failure that require dialysis or clairance creatinine < 30 ml/min
- Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator including:
o NYHA functional classification III or IV congestive heart failure
o LVEF (Left Ventricular Ejection Fraction) < 40%
o Uncontrolled angina, hypertension or arrhythmia
o Myocardial infarction in the past 6 months
- Prior history of malignancies, other than multiple myeloma, unless the patients has been free of the disease for = 5 years. Exceptions include the following:
o Basal or squamous cell carcinoma of the skin
o Carcinoma in situ of the cervix or breast
o Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
- Evidence of central nervous system (CNS) involvement
- Ongoing active infection or other clinically significant uncontrolled cardiovascular events
- Unable to comply with IMids regulation to thromboprophylaxis, or teratogenic recommandations.
- Patients can be exposed to anti CD38 (any), BUT the wash out period for patient pre-treated with an anti CD38 antibody must be of 3 months minimum between last dose of previous anti-CD38 antibody and the first dose of isatuximab.
- Refractory to prior carfilzomib,
- Known allergy to one of the study product (pomalidomide, isatuximab, carfilzomib) or dexamethasone
- Patient with a history of severe allergic reactions to thalidomide or lenalidomide
- Previously exposed to pomalidomide
- Known intolerance to infused protein products, sucrose, histidine, and polysorbate 80
- Contraindications to dexamethasone
- Any ongoing non hematological adverse event or medical history grade> 2 severity
- Pregnant or breast-feeding females
- Refusal to participate in the study
- Persons protected by a legal regime (guardianship, trusteeship)
- Participation in another interventional clinical trial
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to determine the efficacy of Isatuximab, Pomalidomide plus Carfilzomib in early Relapse Refractory Multiple Myleoma according to IMWG*.;Secondary Objective: - To assess the safety according to CTCAE 5.0.<br>- To assess response to the treatment according to IMWG*. <br>- To assess the survival according to IMWG*. <br>;Primary end point(s): MRD 10-5 incidence rate determined at any time point in patients that reached at least VGPR with IsPd +K as per IMWG criteria by NGS ;Timepoint(s) of evaluation of this end point: At any time point during treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1)Treatment emergent adverse events of Isatuximab, Pomalidomide plus Carfilzomib will be evaluated according to CTCAE 5.0.<br>2)To determine Overall Response Rate (ORR, Partial Response and better), Very Good Partial Response (VGPR) + CR rate of IsPd +K as per IMWG criteria and with M protein interference testing.<br>Clinical benefit response rate (CBR, Minor Response (MR) and better) of IsPd +K as per IMWG criteria. <br>3)Time to response and Response duration for responders as per IMWG criteria.<br>4)Overall Survival (OS), Progression free survival (PFS), Time To Progression (TTP), Time To Next Therapy (TTNT) and Event Free survival (EFS) of IsPd +K will be evaluated as per IMWG criteria.<br>;Timepoint(s) of evaluation of this end point: At any time point during treatment