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Completed

NCT Number: NCT01102426

Aplidin - Dexamethasone in Relapsed/Refractory Myeloma

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

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Key information

Conditions

Relapsed/Refractory Multiple Myeloma Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Multiple Myeloma Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

108, Adelaide, Australia

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Plitidepsin

Drug

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 names: APLIDIN (plitidepsin)

Dexamethasone

Drug

4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks.

Other names: DXN

Primary outcomes

  1. 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

  2. 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

Secondary outcomes

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

Sponsors and collaborators

Lead sponsor

PharmaMar

Industry

Registry information

Official study title

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

Acronym: ADMYRE

Important dates

Study start
2010
Primary completion
2017
Study completion
2017
First posted
Apr 13, 2010
Registry last updated
Nov 10, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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