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Aplidin - Dexamethasone in Relapsed/Refractory Myeloma (ADMYRE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01102426
Recruitment Status : Completed
First Posted : April 13, 2010
Results First Posted : October 22, 2020
Last Update Posted : October 22, 2020
Sponsor:
Information provided by (Responsible Party):
PharmaMar

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

Condition or disease Intervention/treatment Phase
Relapsed/Refractory Multiple Myeloma Drug: Plitidepsin Drug: Dexamethasone Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 255 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized, Multicenter, Open-label, Phase III Study of Plitidepsin in Combination With Dexamethasone vs. Dexamethasone Alone in Patients With Relapsed/Refractory Multiple Myeloma
Study Start Date : June 2010
Actual Primary Completion Date : November 2017
Actual Study Completion Date : November 2017


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 Name: APLIDIN (plitidepsin)

Drug: Dexamethasone
4 mg tablet. 40 mg orally on Day 1, 8, 15 and 22 every four weeks.
Other Name: 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 Name: DXN




Primary Outcome Measures :
  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. 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 Outcome Measures :
  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. 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. 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. 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. 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. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01102426


Locations
Show Show 82 study locations
Sponsors and Collaborators
PharmaMar
Investigators
Layout table for investigator information
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 Documents (Full-Text)

Documents provided by PharmaMar:
Study Protocol  [PDF] July 10, 2017
Statistical Analysis Plan  [PDF] June 15, 2017

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Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT01102426    
Other Study ID Numbers: APL-C-001-09
First Posted: April 13, 2010    Key Record Dates
Results First Posted: October 22, 2020
Last Update Posted: October 22, 2020
Last Verified: September 2020
Keywords provided by PharmaMar:
Multiple Myeloma
Aplidin
plitidepsin
dexamethasone
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents