Aplidin - Dexamethasone in Relapsed/Refractory Myeloma (ADMYRE)

October 21, 2020 updated by: PharmaMar

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

255

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Plitidepsin+Dexamethasone
plitidepsin + dexamethasone combination
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 Names:
  • APLIDIN (plitidepsin)
Drug: Dexamethasone
4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks.
Other Names:
  • DXN
Active Comparator: Dexamethasone
dexamethasone single agent
Drug: Dexamethasone
4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks.
Other Names:
  • DXN

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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.
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
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
From randomization to the death due to any cause,assessed up to 5 years
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
From randomization to the death due to any cause,assessed up to 12 months
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
From randomization to the death due to any cause,assessed up to 24 months
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 6 months
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 6 months
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years
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
From the date of first documentation of response to the date of disease progression or death, assessed up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PharmaMar

Investigators

  • 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2010

Primary Completion (Actual)

November 1, 2017

Study Completion (Actual)

November 1, 2017

Study Registration Dates

First Submitted

March 31, 2010

First Submitted That Met QC Criteria

April 12, 2010

First Posted (Estimate)

April 13, 2010

Study Record Updates

Last Update Posted (Actual)

November 10, 2020

Last Update Submitted That Met QC Criteria

October 21, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • APL-C-001-09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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