Melflufen for Elderly Patients With Relapsed Myeloma

Melflufen for Elderly Myeloma Patients in Second or Subsequent Relapse

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.

Study Overview

• Status: Withdrawn
• Conditions: Relapse Multiple Myeloma
• Intervention / Treatment: Drug: Melflufen; Drug: Dexamethasone

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Ancona, Italy
    • A.O.U. delle Marche
  • Legnano, Italy
    • Ospedale Nuovo di Legnano
  • Milano, Italy
    • Ospedale Niguarda
  • Milano, Italy
    • Ospedale S. Carlo Borromeo
  • Palermo, Italy
    • Policlinico Giaccone Divisione Ematologia e Centro Trapianti di Midollo
  • Parma, Italy
    • A.O.U. di Parma
  • Pisa, Italy
    • A.O.U. Pisana
  • San Giovanni Rotondo, Italy
    • I.R.C.C.S. Ospedale Casa Sollievo della Sofferenza
  • Torino, Italy
    • A.O.U. Città della Salute e della Scienza di Torino-SSD Clinical trials
  • Udine, Italy
    • Ospedale S. Maria della Misericordia di Udine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Melflufen and Dexamethasone; 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; Pepaxti 20 mg powder for concentrate for solution for infusion; Drug: Dexamethasone; SOLDESAM 8 mg/2 ml solution for injection SOLDESAM 0.2% oral drops, solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
DURATION OF RESPONSE	the time from the date of first documented response (≥PR) to the date of first confirmed PD.	after 2.5 years
PROGRESSION-FREE SURVIVAL	the time from the date of 1st dose of study drug to the date of first confirmed PD or death due to any cause, whichever occurs first.	after 6 months
TIME TO PROGRESSION	the time from the date of 1st dose of study drug to the date of first documented PD	after 2.5 years
PROGRESSION-FREE SURVIVAL 2	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 that starts after the next line of therapy, whichever occurs first.	after 2.5 years
OVERALL SURVIVAL	the time from the date of 1st dose of study drug to the date of death.	after 2.5 years
TIME TO RESPONSE	the time from the date of 1st dose of study drug to the first documented response (≥PR).	after 2.5 years

Collaborators and Investigators

• Sponsor: Fondazione EMN Italy Onlus

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2025
• Primary Completion (Actual): March 26, 2025
• Study Completion (Actual): March 26, 2025

Study Registration Dates

• First Submitted: November 8, 2024
• First Submitted That Met QC Criteria: November 8, 2024
• First Posted (Actual): November 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 26, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Recurrence; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: MELISSA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No