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Trial record 1 of 1 for:    NCT01102426
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Aplidin - Dexamethasone in Relapsed/Refractory Myeloma (ADMYRE)

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ClinicalTrials.gov Identifier: NCT01102426
Recruitment Status : Completed
First Posted : April 13, 2010
Results First Posted : October 22, 2020
Last Update Posted : November 10, 2020
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Tracking Information
First Submitted Date  ICMJE March 31, 2010
First Posted Date  ICMJE April 13, 2010
Results First Submitted Date  ICMJE July 27, 2020
Results First Posted Date  ICMJE October 22, 2020
Last Update Posted Date November 10, 2020
Study Start Date  ICMJE June 2010
Actual Primary Completion Date November 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
  • Progression Free Survival (PFS) as Per Intention-to-treat (ITT) [ Time Frame: 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 lesions
  • Percentage of Participants With Progression Free Survival (PFS) as Per Intention-to-treat (ITT) at 6 Months [ Time Frame: 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
Original Primary Outcome Measures  ICMJE
 (submitted: April 12, 2010)
Progression Free Survival (PFS) as per intention-to-treat (ITT) [ Time Frame: Estimated average: 5 months. From randomization to the first evidence of progressive disease or death due to any cause ]
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2020)
  • Progression-free Survival (Investigator Assessment) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2010)
  • Response rate [ Time Frame: Every 4 weeks untill progression ]
  • Duration of Response [ Time Frame: Estimated average: 3 months. From the date of first documentation of response to the date of disease progression or death. ]
  • Overall Survival [ Time Frame: Estimated average: 9 months. From randomization to the first evidence of progressive disease or death due to any cause ]
    Overal Survival (OS) is defined as the time from the date of randomization to the date of death or last contact
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Aplidin - Dexamethasone in Relapsed/Refractory Myeloma
Official Title  ICMJE Randomized, Multicenter, Open-label, Phase III Study of Plitidepsin in Combination With Dexamethasone vs. Dexamethasone Alone in Patients With Relapsed/Refractory Multiple Myeloma
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed/Refractory Multiple Myeloma
Intervention  ICMJE
  • 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.
    Other Name: APLIDIN (plitidepsin)
  • Drug: Dexamethasone
    4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks.
    Other Name: DXN
Study Arms  ICMJE
  • Experimental: Plitidepsin+Dexamethasone
    plitidepsin + dexamethasone combination
    Interventions:
    • Drug: Plitidepsin
    • Drug: Dexamethasone
  • Active Comparator: Dexamethasone
    dexamethasone single agent
    Intervention: Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 25, 2020)
255
Original Estimated Enrollment  ICMJE
 (submitted: April 12, 2010)
250
Actual Study Completion Date  ICMJE November 2017
Actual Primary Completion Date November 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Czechia,   France,   Germany,   Greece,   Ireland,   Italy,   Korea, Republic of,   Netherlands,   New Zealand,   Poland,   Portugal,   Puerto Rico,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT01102426
Other Study ID Numbers  ICMJE APL-C-001-09
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PharmaMar
Study Sponsor  ICMJE PharmaMar
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Óscar F. Ballester, M.D. Edwards Comprehensive Cancer Center, Marshall University (Huntington)
Principal Investigator: Rubén Niesvizky, M.D. NY Presbyterian Hosp. - Cornell University - NY
PRS Account PharmaMar
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP