Aplidin - Dexamethasone in Relapsed/Refractory Myeloma

Relapsed/Refractory Multiple Myeloma Clinical Trial

— ADMYRE  

Official title:

Randomized, Multicenter, Open-label, Phase III Study of Plitidepsin in Combination With Dexamethasone vs. Dexamethasone Alone in Patients With Relapsed/Refractory Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01102426
• Other study ID #: APL-C-001-09
• Status: Completed
• Phase: Phase 3
• Start date: June 2010
• Est. completion date: November 2017

Study information

• Verified date: October 2020
• Source: PharmaMar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study of Plitidepsin in combination with dexamethasone versus dexamethasone alone in patients with relapsed/refractory multiple myeloma.

Description:

Phase III Study in Patients with Relapsed/Refractory Multiple Myeloma to compare the efficacy of plitidepsin in combination with dexamethasone vs. dexamethasone alone measured by progression-free survival (PFS) and to evaluate tumor response, duration of response (DR), overall survival (OS) and to rule out any effect of plitidepsin on the duration of the QT/QTc interval (time corresponding to the beginning of depolarization to re-polarization of the ventricles).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 255
• Est. completion date: November 2017
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 2
• Life expectancy = 3 months.
• Patients previously diagnosed with multiple myeloma
• Patients must have relapsed or relapsed and refractory multiple myeloma (MM) after at least three but not more than six prior therapeutic regimens for MM, including induction therapy and stem cell transplant in candidate patients, which will be considered as only one regimen.
• Patients must have received previous bortezomib-containing and lenalidomide-containing regimens (or thalidomide where lenalidomide is not available)
• Women must have a negative serum pregnancy test
• Voluntarily signed and dated written informed consent

Exclusion Criteria:

• Concomitant diseases/conditions
• Women who are pregnant or breast feeding.
• Concomitant medications that include corticosteroids, chemotherapy, or other therapy that is or may be active against MM
• Known hypersensitivity to any involved study drug or any of its formulation components

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Relapsed/Refractory Multiple Myeloma

Intervention

Drug:
• Plitidepsin
plitidepsin: powder and solvent for concentrate for solution for infusion. 2 mg vial + 4 ml ampoule. 5 mg/m2 intravenously (i.v.) over three hours on Day 1 and 15 every 4 weeks. dexamethasone: 4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks at least one hour before plitidepsin infusion.
• Dexamethasone
4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks.

Locations

Country	Name	City	State
Australia	108	Adelaide
Australia	102	Canberra
Australia	101	Geelong
Australia	105	Parkville
Australia	106	Perth
Australia	104	South Brisbane
Australia	109	Woodville
Austria	202	Graz
Austria	204	Innsbruck
Austria	203	Salzburg
Austria	201	Wien
Austria	205	Wien
Austria	208	Wien
Belgium	304	Brugge
Belgium	301	Brussels
Belgium	303	Brussels
Belgium	302	Gent
Czechia	502	Brno
Czechia	503	Hradec Kralove
Czechia	501	Praha
France	601	Lille
France	602	Nantes
France	606	Rouen
France	604	Vandœuvre-lès-Nancy
Germany	709	Düsseldorf
Germany	705	Essen
Germany	706	Frankfurt
Germany	707	Frankfurt
Germany	708	Freiburg
Germany	703	Heidelberg
Germany	702	Munchen
Germany	704	Würzburg
Greece	1301	Athens
Greece	1303	Patras
Greece	1302	Thessaloniki
Ireland	1401	Dublin
Italy	806	Bari
Italy	801	Genova
Italy	805	Reggio Emilia
Italy	803	Rozzano
Italy	804	San Giovanni Rotondo
Italy	802	Torino
Korea, Republic of	1502	Anyang
Korea, Republic of	1501	Daejeon
Korea, Republic of	1507	Hwasun
Korea, Republic of	1506	Incheon
Korea, Republic of	1505	Jeonju
Korea, Republic of	1508	Seongnam
Korea, Republic of	1503	Seoul
Korea, Republic of	1504	Seoul
Korea, Republic of	1509	Seoul
Netherlands	901	Rotterdam
Netherlands	902	Rotterdam
New Zealand	1601	Christchurch
New Zealand	1602	Takapuna
Poland	1704	Opole
Poland	1703	Warszawa
Portugal	1802	Braga
Portugal	1801	Porto
Puerto Rico	2001	San Juan
Spain	1201	Barcelona
Spain	1203	Barcelona
Spain	1209	Barcelona
Spain	1207	Madrid
Spain	1210	Madrid
Spain	1206	Murcia
Spain	1204	Palma de Mallorca
Spain	1208	Salamanca
Spain	1202	San Sebastián
Spain	1205	Valencia
Taiwan	1901	Taipei
Taiwan	1902	Taipei
Taiwan	1903	Taipei
United Kingdom	1003	Bournemouth
United Kingdom	1004	Bradford
United Kingdom	1001	London
United Kingdom	1005	Nottingham
United States	1104	Canton	Ohio
United States	1105	Jacksonville	Florida
United States	1103	Los Angeles	California
United States	1102	New York	New York
United States	1107	Tuscaloosa	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
PharmaMar

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Czechia,  France,  Germany,  Greece,  Ireland,  Italy,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Portugal,  Puerto Rico,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) as Per Intention-to-treat (ITT)	To compare the efficacy of plitidepsin in combination with dexamethasone vs. dexamethasone alone as measured by progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (MM).; Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
Primary	Percentage of Participants With Progression Free Survival (PFS) as Per Intention-to-treat (ITT) at 6 Months	To compare the efficacy of plitidepsin in combination with dexamethasone vs. dexamethasone alone as measured by progression-free survival (PFS) in patients with relapsed/refractory multiple myeloma (MM).; Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Secondary	Progression-free Survival (Investigator Assessment)	The secondary study analysis was based on Investigator's assessment PFS data in the ITT efficacy population, defined as all patients randomized to either treatment arm. PFS was calculated from randomization to the first evidence of PD or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions If the patient received further antitumor therapy before PD and within the timeframe expected for first follow-up, PFS was censored on the date of the last disease assessment prior to the administration of this antitumor therapy.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years
Secondary	Percentage of Participants With Progression-free Survival (Investigator Assessment) at 6 Months	The secondary study analysis was based on Investigator's assessment PFS data in the ITT efficacy population, defined as all patients randomized to either treatment arm. PFS was calculated from randomization to the first evidence of PD or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions If the patient received further antitumor therapy before PD and within the timeframe expected for first follow-up, PFS was censored on the date of the last disease assessment prior to the administration of this antitumor therapy.	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
Secondary	Overall Survival	Overall Survival (OS) is defined as the time from the date of randomization to the date of death or last contact	From randomization to the death due to any cause,assessed up to 5 years
Secondary	Percentage of Participants With Overall Survival at 12 Months	Overall Survival (OS) is defined as the time from the date of randomization to the date of death or last contact	From randomization to the death due to any cause,assessed up to 12 months
Secondary	Percentage of Participants With Overall Survival at 24 Months	Overall Survival (OS) is defined as the time from the date of randomization to the date of death or last contact	From randomization to the death due to any cause,assessed up to 24 months
Secondary	Duration of Response (Independent Review Committee)	DR was calculated from the date of first documentation of response to the date of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
Secondary	Percentage of Participants With Duration of Response (Independent Review Committee) at 6 Months	DR was calculated from the date of first documentation of response to the date of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From the date of first documentation of response to the date of disease progression or death, assessed up to 6 months
Secondary	Duration of Response (Investigator Assessment)	DR was calculated from the date of first documentation of response to the date of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
Secondary	Percentage of Participants With Duration of Response (Investigator Assessment) at 6 Months	DR was calculated from the date of first documentation of response to the date of disease progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	From the date of first documentation of response to the date of disease progression or death, assessed up to 6 months
Secondary	Best Overall Response (Independent Review Committee)	Very good partial response (VGPR) serum and urine M-protein detectable but not electrophoresis or >90% reduction in serum M-protein and urine M-protein <100 mg/24h Partial response (PR) =50% reduction in serum M-protein and 90% reduction in 24h urine M-protein or to <200 mg/24h. 50% reduction in size of any soft tissue plasmacytomas Minor response (MR) 25%-49% reduction of serum M-protein and 50-89% reduction of 24h urine M-protein. 25-49% reduction in size of soft tissue plasmacytomas. No increase in size or number of bone lesions Stable disease (SD) No sCR, CR, VGPR, PR, MR or PD Progressive disease (PD) 25% increase from the lowest value: serum M-protein, urine M-protein, BM plasma cell. Increase in size, new bone lesions, soft tissue plasmacytomas or serum calcium >11.5 mg/dL; NE, not evaluable	From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
Secondary	Overall Response Rate (Independent Review Committee)	Overall response rate including sCR, CR, VGPR, PR and MR. Very good partial response (VGPR) serum and urine M-protein detectable but not electrophoresis or >90% reduction in serum M-protein and urine M-protein <100 mg/24h Partial response (PR) =50% reduction in serum M-protein and 90% reduction in 24h urine M-protein or to <200 mg/24h. 50% reduction in size of any soft tissue plasmacytomas Minor response (MR) 25%-49% reduction of serum M-protein and 50-89% reduction of 24h urine M-protein. 25-49% reduction in size of soft tissue plasmacytomas. No increase in size or number of bone lesions	From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
Secondary	Overall Response Rate (Independent Review Committee) Excluding MR	Includes sCR, CR, VGPR and PR (excludes MR). Very good partial response (VGPR) serum and urine M-protein detectable but not electrophoresis or >90% reduction in serum M-protein and urine M-protein <100 mg/24h Partial response (PR) =50% reduction in serum M-protein and 90% reduction in 24h urine M-protein or to <200 mg/24h. 50% reduction in size of any soft tissue plasmacytomas	From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
Secondary	Best Overall Response (Investigator Assessment)	Very good partial response (VGPR) serum and urine M-protein detectable but not electrophoresis or >90% reduction in serum M-protein and urine M-protein <100 mg/24h Partial response (PR) =50% reduction in serum M-protein and 90% reduction in 24h urine M-protein or to <200 mg/24h. 50% reduction in size of any soft tissue plasmacytomas Minor response (MR) 25%-49% reduction of serum M-protein and 50-89% reduction of 24h urine M-protein. 25-49% reduction in size of soft tissue plasmacytomas. No increase in size or number of bone lesions Stable disease (SD) No sCR, CR, VGPR, PR, MR or PD Progressive disease (PD) 25% increase from the lowest value: serum M-protein, urine M-protein, BM plasma cell. Increase in size, new bone lesions, soft tissue plasmacytomas or serum calcium >11.5 mg/dL; NE, not evaluable	From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
Secondary	Overall Response Rate (Investigator Assessment)	Includes sCR, CR, VGPR, PR and MR. Very good partial response (VGPR) serum and urine M-protein detectable but not electrophoresis or >90% reduction in serum M-protein and urine M-protein <100 mg/24h Partial response (PR) =50% reduction in serum M-protein and 90% reduction in 24h urine M-protein or to <200 mg/24h. 50% reduction in size of any soft tissue plasmacytomas Minor response (MR) 25%-49% reduction of serum M-protein and 50-89% reduction of 24h urine M-protein. 25-49% reduction in size of soft tissue plasmacytomas. No increase in size or number of bone lesions	From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
Secondary	Overall Response Rate (Investigator Assessment) Excluding MR	Very good partial response (VGPR) serum and urine M-protein detectable but not electrophoresis or >90% reduction in serum M-protein and urine M-protein <100 mg/24h Partial response (PR) =50% reduction in serum M-protein and 90% reduction in 24h urine M-protein or to <200 mg/24h. 50% reduction in size of any soft tissue plasmacytomas	From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years