Clinical trial NCT06682637: Melflufen for Elderly Patients With Relapsed Myeloma
Official title: Melflufen for Elderly Myeloma Patients in Second or Subsequent Relapse
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Relapse Multiple Myeloma
Lead sponsor: Fondazione EMN Italy Onlus
Sponsor class: OTHER
First posted: 2024-11-12
Enrollment: 0
Sex: ALL
Minimum age (years): 70
Maximum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Treatment consists in 28-day cycles:

* Melflufen 40 mg total dose (30 mg in patients with body weight ≤60 kg and/or in patients with eGFR\<45 mL/min) intravenously on day 1.
* Dexamethasone 10 mg orally or intravenously on day 1-2, 8-9, 15-16, 22-23. Cycles are repeated until clinical relapse or progression, or unacceptable toxicity.
Primary purpose: OTHER

Brief summary: This is a pilot study aimed to evaluate the efficacy and tolerability of melflufen plus dexamethasone in elderly patients at second relapse.

Thirty elderly patients at second or subsequent relapse.


Eligibility criteria: Inclusion Criteria:

* Patients affected by MM progressed or relapsed after 2 or more previous lines of therapy.
* Patient is, in the investigator's opinion, willing and able to comply with the study visits and procedures required per protocol.
* 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.
* Life expectancy ≥ 3 months
* Previous exposure to, at least, one drug of all the following categories: an anti-CD38 MoAbs, an IMiD, and a proteasome inhibitor.
* Age ≥ 70 and ≤ 85 years.
* ECOG performance status ≤2.
* 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.
* LVEF ≥40% as determined by a MUGA scan or ECHO.
* Adequate hepatic function characterized by the following:

oTotal bilirubin ≤1.5 x ULN. oAST ≤2.5 x ULN oALT ≤2.5 x ULN.

* 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).
* Adequate BM function characterized by the following:

  * Absolute neutrophil count ≥1.0 × 109/L (use of granulocyte-colony stimulating factors is permitted if completed at least 7 days prior to planned start of dosing).
  * Platelet count ≥50 × 109/L (transfusion support is not permitted).
  * Hemoglobin ≥8 g/dL (transfusion support is permitted).
* Non-vasectomized male patients agree to practice appropriate methods of birth control

Exclusion Criteria:

* 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.
* Plasma cell leukemia.
* Systemic amyloid light chain amyloidosis.
* POEMS Syndrome.
* Central Nervous System (CNS) disease localization.
* Subject with another tumor, not including MM, that required ongoing treatment or therapy completed less than 6 months before eligibility confirmation, and considered at substantial risk of relapse in the following 12 months.
* 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.
* 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.
* Subject has clinically significant cardiac disease, including:

  * Myocardial infarction within 6 months before trial eligibility
  * Uncontrolled disease/condition related to or affecting cardiac function (e.g. unstable angina, congestive heart failure, New York Heart Association Class III-IV)
  * Clinically significant ECG abnormalities.

Primary outcomes:
measure: Overall Response Rate
timeFrame: approximately 6 months after the enrolled of the last participant and an updated analysis will be conducted at approximately 8 to 12 months.
Secondary outcomes:
measure: DURATION OF RESPONSE
timeFrame: after 2.5 years
measure: PROGRESSION-FREE SURVIVAL
timeFrame: after 6 months
measure: TIME TO PROGRESSION
timeFrame: after 2.5 years
measure: PROGRESSION-FREE SURVIVAL 2
timeFrame: after 2.5 years
measure: OVERALL SURVIVAL
timeFrame: after 2.5 years
measure: TIME TO RESPONSE
timeFrame: after 2.5 years
Other outcomes:
Locations:
city: Ancona
country: Italy
facility: A.O.U. delle Marche
city: Legnano
country: Italy
facility: Ospedale Nuovo di Legnano
city: Milano
country: Italy
facility: Ospedale Niguarda
city: Milano
country: Italy
facility: Ospedale S. Carlo Borromeo
city: Palermo
country: Italy
facility: Policlinico Giaccone Divisione Ematologia e Centro Trapianti di Midollo
city: Parma
country: Italy
facility: A.O.U. di Parma
city: Pisa
country: Italy
facility: A.O.U. Pisana
city: San Giovanni Rotondo
country: Italy
facility: I.R.C.C.S. Ospedale Casa Sollievo della Sofferenza
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino-SSD Clinical trials
city: Udine
country: Italy
facility: Ospedale S. Maria della Misericordia di Udine
Study officials:
References: