Melflufen for Elderly Patients with Relapsed Myeloma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-02-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Oncopeptides

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Evaluate the efficacy of melflufen plus dexamethasone in elderly patients at second or subsequent relapse.

Secondary objectives 8

1. Progression-free survival (PFS)
2. Duration of response (DoR)
3. Overall survival (OS)
4. Incidence of all grade cytopenias during the entire duration of the study
5. Discontinuation of treatment due to adverse effects
6. Grade ≥1 adverse events
7. Mortality due to therapy-related adverse events
8. Quality of life (evaluated by QLQ-C30 and QLQ-MY20)

Conditions and MedDRA coding

Relapsed Multiple Myeloma

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 19

1. Patients affected by MM progressed or relapsed after 2 or more previous lines of therapy
2. Patient is, in the investigator’s opinion, willing and able to comply with the study visits and procedures required per protocol
3. 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
4. Life expectancy ≥ 3 months
5. Previous exposure to, at least, one drug of all the following categories: an anti-CD38 MoAbs, an IMiD, and a proteasome inhibitor
6. Age ≥ 70 and ≤ 85 years
7. ECOG performance status ≤2
8. 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
9. LVEF ≥40% as determined by a MUGA scan or ECHO
10. Adequate hepatic function characterized by the following:
11. 1) Total bilirubin ≤1.5 x ULN
12. 2) AST ≤2.5 x ULN
13. 3) ALT ≤2.5 x ULN
14. 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)
15. Adequate BM function characterized by the following:
16. 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)
17. 2) Platelet count ≥50 × 10^9/L (transfusion support is not permitted)
18. 3) Hemoglobin ≥8 g/dL (transfusion support is permitted)
19. Non-vasectomized male patients agree to practice appropriate methods of birth control

Exclusion criteria 12

1. 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
2. Plasma cell leukemia
3. Systemic amyloid light chain amyloidosis
4. POEMS Syndrome
5. Central Nervous System (CNS) disease localization
6. 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
7. 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
8. 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
9. Subject has clinically significant cardiac disease, including:
10. 1) Myocardial infarction within 6 months before trial eligibility
11. 2) Uncontrolled disease/condition related to or affecting cardiac function (e.g. unstable angina, congestive heart failure, New York Heart Association Class III-IV)
12. 3) Clinically significant ECG abnormalities

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 6

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Via Saluzzo 1 A

City

Turin

Postcode

10125

Country

Italy

Scientific contact point

Organisation

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

Contact name

Vittorio Montefusco

Public contact point

Organisation

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

Contact name

Mario Boccadoro

Third parties 1

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 23 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications