Melflufen for Elderly Patients With Relapsed Myeloma

NCT06682637 | Withdrawn Phase 2

• 1 other identifier: MELISSA
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 10

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.

Conditions

Relapse Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  rate of participants who achieve a PR or better (PR+VGPR+CR+sCR) according to IMWG response criteria during the treatment.

  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 (6)

• DURATION OF RESPONSE

  after 2.5 years

• PROGRESSION-FREE SURVIVAL

  after 6 months

• TIME TO PROGRESSION

  after 2.5 years

• PROGRESSION-FREE SURVIVAL 2

  after 2.5 years

• OVERALL SURVIVAL

  after 2.5 years

Study Arms (1)

Melflufen and Dexamethasone

EXPERIMENTAL

* 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.

Drug: Melflufen; Drug: Dexamethasone

Interventions

Melflufen DRUG

Pepaxti 20 mg powder for concentrate for solution for infusion

Melflufen and Dexamethasone

Dexamethasone DRUG

SOLDESAM 8 mg/2 ml solution for injection SOLDESAM 0.2% oral drops, solution

Melflufen and Dexamethasone

Eligibility Criteria

• Age: 70 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione EMN Italy Onlus: lead

Study Sites (10)

A.O.U. delle Marche

Ancona, Italy

Location

Ospedale Nuovo di Legnano

Legnano, Italy

Location

Ospedale Niguarda

Milan, Italy

Location

Ospedale S. Carlo Borromeo

Milan, Italy

Location

Policlinico Giaccone Divisione Ematologia e Centro Trapianti di Midollo

Palermo, Italy

Location

A.O.U. di Parma

Parma, Italy

Location

A.O.U. Pisana

Pisa, Italy

Location

I.R.C.C.S. Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Italy

Location

A.O.U. Città della Salute e della Scienza di Torino-SSD Clinical trials

Torino, Italy

Location

Ospedale S. Maria della Misericordia di Udine

Udine, Italy

Location

MeSH Terms

Interventions

melflufen; Dexamethasone

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: November 12, 2024
• Study Start: March 26, 2025
• Primary Completion: March 26, 2025
• Study Completion: March 26, 2025
• Last Updated: April 1, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (10)