Aplidin - Dexamethasone in Relapsed/Refractory Myeloma
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT01102426
- Lead Sponsor
- PharmaMar
- Brief Summary
Study of Plitidepsin in combination with dexamethasone versus dexamethasone alone in patients with relapsed/refractory multiple myeloma.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 255
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dexamethasone Dexamethasone dexamethasone single agent Plitidepsin+Dexamethasone Dexamethasone plitidepsin + dexamethasone combination Plitidepsin+Dexamethasone Plitidepsin plitidepsin + dexamethasone combination
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) as Per Intention-to-treat (ITT) 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 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 lesionsPercentage of Participants With Progression Free Survival (PFS) as Per Intention-to-treat (ITT) at 6 Months 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 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
- Secondary Outcome Measures
Name Time Method Progression-free Survival (Investigator Assessment) 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 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.
Percentage of Participants With Progression-free Survival (Investigator Assessment) at 6 Months 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 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.
Overall Survival From randomization to the death due to any cause,assessed up to 5 years Overall Survival (OS) is defined as the time from the date of randomization to the date of death or last contact
Percentage of Participants With Overall Survival at 12 Months From randomization to the death due to any cause,assessed up to 12 months Overall Survival (OS) is defined as the time from the date of randomization to the date of death or last contact
Percentage of Participants With Overall Survival at 24 Months From randomization to the death due to any cause,assessed up to 24 months Overall Survival (OS) is defined as the time from the date of randomization to the date of death or last contact
Duration of Response (Independent Review Committee) From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years 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
Percentage of Participants With Duration of Response (Independent Review Committee) at 6 Months From the date of first documentation of response to the date of disease progression or death, assessed up to 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
Duration of Response (Investigator Assessment) From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years 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
Percentage of Participants With Duration of Response (Investigator Assessment) at 6 Months From the date of first documentation of response to the date of disease progression or death, assessed up to 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
Best Overall Response (Independent Review Committee) From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years 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
Overall Response Rate (Independent Review Committee) From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years 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
Overall Response Rate (Independent Review Committee) Excluding MR From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years 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
Best Overall Response (Investigator Assessment) From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years 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
Overall Response Rate (Investigator Assessment) From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years 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
Overall Response Rate (Investigator Assessment) Excluding MR From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years 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
Trial Locations
- Locations (82)
1003
🇬🇧Bournemouth, United Kingdom
201
🇦🇹Wien, Austria
1102
🇺🇸New York, New York, United States
302
🇧🇪Gent, Belgium
304
🇧🇪Brugge, Belgium
706
🇩🇪Frankfurt, Germany
708
🇩🇪Freiburg, Germany
602
🇫🇷Nantes, France
108
🇦🇺Adelaide, Australia
105
🇦🇺Parkville, Australia
301
🇧🇪Brussels, Belgium
801
🇮🇹Genova, Italy
1503
🇰🇷Seoul, Korea, Republic of
702
🇩🇪Munchen, Germany
202
🇦🇹Graz, Austria
1507
🇰🇷Hwasun, Korea, Republic of
204
🇦🇹Innsbruck, Austria
205
🇦🇹Wien, Austria
1303
🇬🇷Patras, Greece
806
🇮🇹Bari, Italy
501
🇨🇿Praha, Czechia
503
🇨🇿Hradec Kralove, Czechia
1401
🇮🇪Dublin, Ireland
803
🇮🇹Rozzano, Italy
1505
🇰🇷Jeonju, Korea, Republic of
707
🇩🇪Frankfurt, Germany
601
🇫🇷Lille, France
606
🇫🇷Rouen, France
703
🇩🇪Heidelberg, Germany
1601
🇳🇿Christchurch, New Zealand
705
🇩🇪Essen, Germany
804
🇮🇹San Giovanni Rotondo, Italy
1502
🇰🇷Anyang, Korea, Republic of
1506
🇰🇷Incheon, Korea, Republic of
1704
🇵🇱Opole, Poland
805
🇮🇹Reggio Emilia, Italy
604
🇫🇷Vandœuvre-lès-Nancy, France
1504
🇰🇷Seoul, Korea, Republic of
104
🇦🇺South Brisbane, Australia
1103
🇺🇸Los Angeles, California, United States
1104
🇺🇸Canton, Ohio, United States
1107
🇺🇸Tuscaloosa, Alabama, United States
1105
🇺🇸Jacksonville, Florida, United States
102
🇦🇺Canberra, Australia
101
🇦🇺Geelong, Australia
106
🇦🇺Perth, Australia
109
🇦🇺Woodville, Australia
208
🇦🇹Wien, Austria
303
🇧🇪Brussels, Belgium
502
🇨🇿Brno, Czechia
709
🇩🇪Düsseldorf, Germany
1302
🇬🇷Thessaloniki, Greece
1301
🇬🇷Athens, Greece
704
🇩🇪Würzburg, Germany
802
🇮🇹Torino, Italy
1501
🇰🇷Daejeon, Korea, Republic of
1508
🇰🇷Seongnam, Korea, Republic of
1509
🇰🇷Seoul, Korea, Republic of
902
🇳🇱Rotterdam, Netherlands
901
🇳🇱Rotterdam, Netherlands
1602
🇳🇿Takapuna, New Zealand
1802
🇵🇹Braga, Portugal
1201
🇪🇸Barcelona, Spain
1801
🇵🇹Porto, Portugal
2001
🇵🇷San Juan, Puerto Rico
1001
🇬🇧London, United Kingdom
1203
🇪🇸Barcelona, Spain
1209
🇪🇸Barcelona, Spain
1210
🇪🇸Madrid, Spain
1207
🇪🇸Madrid, Spain
1206
🇪🇸Murcia, Spain
1204
🇪🇸Palma de Mallorca, Spain
1208
🇪🇸Salamanca, Spain
1202
🇪🇸San Sebastián, Spain
1205
🇪🇸Valencia, Spain
1901
🇨🇳Taipei, Taiwan
1902
🇨🇳Taipei, Taiwan
1903
🇨🇳Taipei, Taiwan
1004
🇬🇧Bradford, United Kingdom
1005
🇬🇧Nottingham, United Kingdom
203
🇦🇹Salzburg, Austria
1703
🇵🇱Warszawa, Poland