melphalan flufenamide for Multiple myeloma | Relapsed/refractory multiple myeloma

Inclusion criteria

• {"criterion_text":"- Patients affected by MM progressed or relapsed after 2 or more previous lines of therapy\n- Adequate hepatic function characterized by the following:\n- 1) Total bilirubin ≤1.5 x ULN\n- 2) AST ≤2.5 x ULN\n- 3) ALT ≤2.5 x ULN\n- Estimated creatinine clearance ≥30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or per the local institutional standard method)\n- Adequate BM function characterized by the following:\n- 1) Absolute neutrophil count ≥1.0 × 10^9/L (use of granulocyte-colony stimulating factors is permitted if completed at least 7 days prior to planned start of dosing)\n- 2) Platelet count ≥50 × 10^9/L (transfusion support is not permitted)\n- 3) Hemoglobin ≥8 g/dL (transfusion support is permitted)\n- Non-vasectomized male patients agree to practice appropriate methods of birth control\n- Patient is, in the investigator’s opinion, willing and able to comply with the study visits and procedures required per protocol\n- Patient has provided written informed consent in accordance with federal, local, and institutional guidelines prior to initiation of any study-specific activities or procedures. Subject does not have kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent and patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements\n- Life expectancy ≥ 3 months\n- Previous exposure to, at least, one drug of all the following categories: an anti-CD38 MoAbs, an IMiD, and a proteasome inhibitor\n- Age ≥ 70 and ≤ 85 years\n- ECOG performance status ≤2\n- Subject must have serum monoclonal paraprotein (M-protein) level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours, or serum immunoglobulin involved free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio\n- LVEF ≥40% as determined by a MUGA scan or ECHO"}

Exclusion criteria

• {"criterion_text":"- Previous exposure to chemotherapy (i.e. melphalan, high-dose melphalan and/or cyclophosphamide) with the exception of patients who have received an autologous stem cell transplantion with a progression free survival of at least 36 month\n- 1) Myocardial infarction within 6 months before trial eligibility\n- 2) Uncontrolled disease/condition related to or affecting cardiac function (e.g. unstable angina, congestive heart failure, New York Heart Association Class III-IV)\n- 3) Clinically significant ECG abnormalities\n- Plasma cell leukemia\n- Systemic amyloid light chain amyloidosis\n- POEMS Syndrome\n- Central Nervous System (CNS) disease localization\n- Subject with another tumor, not including MM, that required ongoing treatment or therapy completed less than 6 months before, and considered at substantial risk of relapse in the following 12 months\n- Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to eligibility confirmation\n- Subject has any concurrent medical condition or disease (e.g. 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\n- Subject has clinically significant cardiac disease, including:"}

Primary endpoints

• {"endpoint_text":"- It is the overall response rate anytime during the treatment period. Overall response rate (ORR) is defined as participants who achieve a PR or better (PR+VGPR+CR+sCR) according to IMWG response criteria during the treatment. The primary estimand is defined by the 5 components: Treatment, Population, Variable, Population-levels summary, Intercurrent event. It will be considered reached if >7 PR or better are present.Rate and the corresponding 90% Clopper-Pearson exact CI will be also provided.","definition_or_measurement_approach":"Overall response rate (ORR) defined as participants who achieve a PR or better (PR+VGPR+CR+sCR) according to IMWG response criteria during the treatment. The primary estimand is defined by Treatment, Population, Variable, Population-level summary, Intercurrent event. Success criterion: >7 participants with PR or better. Rate and 90% Clopper-Pearson exact CI will be provided."}

Secondary endpoints

• {"endpoint_text":"- Duration of response (DOR) is defined as the time from the date of first documented response (≥PR) to the date of first confirmed PD. If the participant is w/o progression disease, the participant’s data will be censored at the date of last disease assessment.","definition_or_measurement_approach":"Time from first documented response (≥PR) to first confirmed disease progression (PD); censor at date of last disease assessment if no progression."}
• {"endpoint_text":"- Progression-free survival (PFS) is defined as the time from the date of 1st dose of study drug to the date of first confirmed PD, as defined in the IMWG response criteria, or death due to any cause, whichever occurs first. If the participant is alive and w/o progression disease, the participant’s data will be censored at the date of last disease assessment.","definition_or_measurement_approach":"Time from first dose to first confirmed PD (per IMWG) or death; censored at last disease assessment if alive and without progression."}
• {"endpoint_text":"- Time to progression (TTP) is defined as the time from the date of 1st dose of study drug to the date of first documented PD, as defined in the IMWG response criteria. If the participant is w/o progression disease or die, the participant’s data will be censored at the date of last disease assessment.","definition_or_measurement_approach":"Time from first dose to first documented PD (per IMWG); censor at last disease assessment if no progression or death."}
• {"endpoint_text":"- Progression free survival 2 (PFS2) is defined as the time from the date of 1st dose of study drug to the date of event, which is defined as death from any cause or PD as assessed by investigator that starts after the next line of therapy, whichever occurs first.","definition_or_measurement_approach":"Time from first dose to death or investigator-assessed PD that occurs after the next line of therapy; whichever occurs first."}
• {"endpoint_text":"- Overall survival (OS) is defined as the time from the date of 1st dose of study drug to the date of death. If the participant is alive, the participant’s data will be censored at the date the participant was last known to be alive.","definition_or_measurement_approach":"Time from first dose to death; censor at last known alive date."}
• {"endpoint_text":"- Time to response (TTR) is defined as the time from the date of 1st dose of study drug to the first documented response (≥PR). If the participant is alive, w/o progression disease and w/o documented response (≥PR), the participant’s data will be censored at the date of last disease assessment. If the participant have a progression or die before a documented response (≥PR), the participant’s data will have a competing event at the date of PFS event.","definition_or_measurement_approach":"Time from first dose to first documented response (≥PR); censor at last disease assessment if no response and alive without progression; progression or death before response treated as competing event."}

Italy

Earliest CTIS Part Ii Submission Date

07-01-2025

Latest Decision Or Authorization Date

12-02-2025

Processing Time Days

36

Number Of Sites

10

Number Of Participants

30

Primary sponsor

Full Name

Fondazione European Myeloma Network Italy O.N.L.U.S.

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy

Third parties

• {"country":"Italy","full_name":"Depo-pack S.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}