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)
1107
🇺🇸Tuscaloosa, Alabama, United States
1103
🇺🇸Los Angeles, California, United States
1105
🇺🇸Jacksonville, Florida, United States
1102
🇺🇸New York, New York, United States
1104
🇺🇸Canton, Ohio, United States
108
🇦🇺Adelaide, Australia
102
🇦🇺Canberra, Australia
101
🇦🇺Geelong, Australia
105
🇦🇺Parkville, Australia
106
🇦🇺Perth, Australia
Scroll for more (72 remaining)1107🇺🇸Tuscaloosa, Alabama, United States