PORT: A Randomized, Cross-Over, Phase 2 Study of Melflufen Peripheral Versus Central Intravenous Administration in Patients With Relapsed/Refractory Multiple Myeloma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F24%3A00079838" target="_blank" >RIV/65269705:_____/24:00079838 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/24:73624775 RIV/00098892:_____/24:10158738

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S2152265024000910?pes=vor" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2152265024000910?pes=vor</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.clml.2024.02.012" target="_blank" >10.1016/j.clml.2024.02.012</a>

Jazyk výsledku

angličtina

Název v původním jazyce

PORT: A Randomized, Cross-Over, Phase 2 Study of Melflufen Peripheral Versus Central Intravenous Administration in Patients With Relapsed/Refractory Multiple Myeloma

Popis výsledku v původním jazyce

Melflufen infusion is given via central venous catheter (CVC); however, use of a peripheral venous catheter (PVC) may be preferable. This study provides data on pharmacokinetics, safety, and tolerability of PVC versus CVC melflufen administration. Melphalan exposure following PVC and CVC administration was bioequivalent; PVC administration was well tolerated, providing support for this route for melflufen administration in future studies. Background: Melflufen, a first-in-class alkylating peptide-drug conjugate, rapidly enters tumor cells and metabolizes to melphalan. In previous studies, melflufen was administered via central venous catheter (CVC). However, administration by peripheral venous catheter (PVC) may be preferable. Patients and Methods: PORT was a two-period, phase 2 crossover study of CVC versus PVC melflufen administration in patients with relapsed/refractory multiple myeloma. Adults with &gt;= 2 prior therapies refractory to/intolerant of an immunomodulatory drug and a proteasome inhibitor were randomized 1:1 to weekly oral dexamethasone plus melflufen (40 mg) via CVC or PVC infusion on day 1 of 28-day cycle 1. In cycle 2, patients continued dexamethasone and crossed over to the other melflufen administration route. In cycle 3, all patients received melflufen until progression; PVC or CVC routes were allowed based upon investigator decision. Pharmacokinetic sampling was performed during and after melflufen infusion. Primary endpoints were melphalan pharmacokinetic parameters (Cmax , AUC(0-t) , and AUC(0- infinity ) ) and frequency and severity of PVC-related local reactions. Results: The 90% CIs for adjusted geometric mean ratios for pharmacokinetic parameters following CVC versus PVC administration were within the 0.8-1.25 bioequivalence range (Cmax 0.946 [90% CI: 0.849, 1.053]; AUC(0-t) 0.952 [90% CI: 0.861, 1.053]; AUC(0- infinity ) 0.955 [90% CI: 0.863, 1.058]). In both arms, adverse events were pr imar ily hematological and similar; no phlebitis or local infusion-related reactions occurred. Conclusion: Melflufen PVC and CVC administrations are bioequivalent based on melphalan pharmacokinetic parameters. Melflufen via PVC was well tolerated, with no infusion-related reactions or new safety signals and may represent an alternative route of administration.

Název v anglickém jazyce

PORT: A Randomized, Cross-Over, Phase 2 Study of Melflufen Peripheral Versus Central Intravenous Administration in Patients With Relapsed/Refractory Multiple Myeloma

Popis výsledku anglicky

Melflufen infusion is given via central venous catheter (CVC); however, use of a peripheral venous catheter (PVC) may be preferable. This study provides data on pharmacokinetics, safety, and tolerability of PVC versus CVC melflufen administration. Melphalan exposure following PVC and CVC administration was bioequivalent; PVC administration was well tolerated, providing support for this route for melflufen administration in future studies. Background: Melflufen, a first-in-class alkylating peptide-drug conjugate, rapidly enters tumor cells and metabolizes to melphalan. In previous studies, melflufen was administered via central venous catheter (CVC). However, administration by peripheral venous catheter (PVC) may be preferable. Patients and Methods: PORT was a two-period, phase 2 crossover study of CVC versus PVC melflufen administration in patients with relapsed/refractory multiple myeloma. Adults with &gt;= 2 prior therapies refractory to/intolerant of an immunomodulatory drug and a proteasome inhibitor were randomized 1:1 to weekly oral dexamethasone plus melflufen (40 mg) via CVC or PVC infusion on day 1 of 28-day cycle 1. In cycle 2, patients continued dexamethasone and crossed over to the other melflufen administration route. In cycle 3, all patients received melflufen until progression; PVC or CVC routes were allowed based upon investigator decision. Pharmacokinetic sampling was performed during and after melflufen infusion. Primary endpoints were melphalan pharmacokinetic parameters (Cmax , AUC(0-t) , and AUC(0- infinity ) ) and frequency and severity of PVC-related local reactions. Results: The 90% CIs for adjusted geometric mean ratios for pharmacokinetic parameters following CVC versus PVC administration were within the 0.8-1.25 bioequivalence range (Cmax 0.946 [90% CI: 0.849, 1.053]; AUC(0-t) 0.952 [90% CI: 0.861, 1.053]; AUC(0- infinity ) 0.955 [90% CI: 0.863, 1.058]). In both arms, adverse events were pr imar ily hematological and similar; no phlebitis or local infusion-related reactions occurred. Conclusion: Melflufen PVC and CVC administrations are bioequivalent based on melphalan pharmacokinetic parameters. Melflufen via PVC was well tolerated, with no infusion-related reactions or new safety signals and may represent an alternative route of administration.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinical Lymphoma Myeloma &amp; Leukemia

ISSN

2152-2650

e-ISSN

2152-2669

Svazek periodika

24

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

11

Strana od-do

"e267"-"e275.e2"

Kód UT WoS článku

001249566600001

EID výsledku v databázi Scopus

2-s2.0-85187982904