Relapsed Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: SOLDESAM - 0.2% GOCCE ORALI, SOLUZIONE FLACONE 10 ML
Product Name: Soldesam
Product Code: [NA]
Pharmaceutical Form: Oral drops
INN or Proposed INN: DESAMETASONE
CAS Number: 50-02-2
Current
Sponsors
EMN RESEARCH ITALY IMPRESA SOCIALE S.R.L.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: a) Patient has given voluntary written informed consent b) Patient is willing and able to comply with the study visits and procedures required per protocol c) Subject must have at least 18 and = 70 years of age d) Patient has a life-expectancy = 3 months e) Subject has received an ASCT in the first line of therapy with a progression/relapse after at least 24 months f) Subject must have received any cytoreductive treatment, excluding anti-CD38 antibodies containing regimens, as per local practice for the first relapse, according to local guidelines. Carfilzomib-based combinations are recommended (eg. carfilzomib-lenalidomide-dexamethasone or carfilzomib-dexamethasone). After the salvage duration phase (reinduction therapy), subject has achieved at least a PR according to IMWG Response criteria. g) Subject must have documented relapsed MM as per IMWG criteria, and achieved at least a partial remission with treatments as per local guidelines h) Subject must have at least 2.0 x 106 CD34+/Kg cryopreserved autologous stem cells i) Subject must have an ECOG Performance Status score of 0, 1 j) Subject must have the following laboratory values: o Platelet count =50 x 109/L (=30 x 109 /L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to drug administration) o Absolute neutrophil count (ANC) = 1 x 109/L without the use of growth factors o Corrected serum calcium =14 mg/dL (3.5 mmol/L) o Alanine transaminase (ALT): = 3 x the ULN o Total bilirubin: = 2 x the ULN o Calculated or measured creatinine clearance: = 30 mL/minute k) Female subjects are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions applies: o they are not females of childbearing potential (FCBP), OR o they are FCBP who 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 before each cycle of study treatment and must either commit to continue abstinence from heterosexual intercourse or apply a highly effective method of birth control during the intervention period and for at least 5 months after the last dose of study treatment. Of note: contraception duration should take also into consideration any backbone therapy l) Male subjects must agree to use contraception on 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 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1. Previous therapy with daratumumab, isatuximab or any other anti-CD38 monoclonal antibody 2. MM localization to the central nervous system 3. Subjects who have received any investigational drug within 14 days or 5 half-lives of the investigational drug from eligibility confirmation, whichever is longer. In case of very aggressive disease, delay could be shortened after agreement between Sponsor and Investigator, in absence of residual toxicities from previous therapy 4. Subjects who have received an allogeneic stem cell transplant 5. Subject with a history of malignancy (other than multiple myeloma) within 3 years before the date of eligibility confirmation (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, in agreement with the medical monitor, is considered cured with minimal risk of recurrence within 3 years) 6. Subject is known to be seropositive for human immunodeficiency virus (HIV) or with an active hepatitis A, B and C infection, defined as a positive test for hepatitis B surface antigen [HBsAg] and a positivity for HAV-RNA, HBV-DNA or HCV-RNA. Uncontrolled or active HBV infection: patients with positive HBsAg and/or HBV DNA. Of note: • Subjects can be eligible if: anti-HBc IgG is positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. If anti-HBV therapy in relation with prior infection was started before initiation of study treatment, the anti-HBV therapy and monitoring should continue throughout the study treatment period. • Subjects with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met. Active HCV infection: positive HCV RNA and negative anti-HCV. Of note: • Subjects with antiviral therapy for HCV started before initiation of study treatment and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion. • Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible. 7. Subject with any concurrent, clinically significant, uncontrolled medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study 8. Subject with active tuberculosis and systemic or severe infections requiring treatment with an antibiotic parenteral administration 9. Subject with hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H1 blockers or would prohibit further treatment with these agents 10. Subject with pulmonary deficit, defined as FEV1 <65% and/or DLCO <65% 11. Subject with clinically significant cardiac disease, including: o LVEF <50% o Myocardial infarction within 6 months before eligibility confirmation, or unstable or o Uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV) o Cardiac arrh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is the evaluation of isatuximab and salvage ASCT efficacy.;Secondary Objective: The secondary objectives are the evaluation of isatuximab and salvage ASCT additional efficacy parameters, safety, and response related features. The exploratory objectives consist in the biological study that is detailed in the “Correlative biological study” section.;Primary end point(s): The rate of MRD negativity is determined as the proportion of patients with NGF MRD negativity (10-5 sensitivity level) within 12 months after ASCT using the intention-to-treat principle. For patients who withdraw from the study or are lost to follow up before this timepoint, the best MRD assessment will be considered. Patients will be classified as MRD positive if they have only MRD positive test results or do not undergo MRD assessment.;Timepoint(s) of evaluation of this end point: Within 12 months after ASCT. For patients who withdraw from the study or are lost to follow up before this timepoint, the best MRD assessment will be considered. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Response rate (sCR, CR, VGPR, PR, ORR) will be evaluated according to IMWG Response criteria after induction, transplant and maintenance. Time to progression (TTP). Progression free survival (PFS). Time to the next anti-myeloma therapy (TNT). Progression free survival 2 (PFS2). Overall survival (OS). Duration of response (DOR). Time to PR, VGPR, CR and sCR. Rate of 1 year sustained MRD negativity by NGF and correlation with PFS and OS. The rate of MRD negativity by NGF (10-5 sensitivity level) within 12 and 24 months after ASCT. Safety (adverse events according to NCI-CTCAE v.5.0). Dose reduction, discontinuation and relative dose.;Timepoint(s) of evaluation of this end point: After induction, transplant and maintenance. | — |
Countries
Italy
Contacts
Public ContactClinical Trial Office
EMN Research Italy Impresa Sociale S.r.l.
Outcome results
None listed