Randomized, Multicenter, Open-label, Phase III Study of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Patients with Relapsed/Refractory Multiple Myeloma - ADMYRE: Aplidin - Dexamethasone in RElapsed/Refractory MYeloma

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2009-016138-29-IT
• Date of registration: 21/05/2010
• Prospective Registration: No
• Primary sponsor: PHARMA MAR
• Public title: Randomized, Multicenter, Open-label, Phase III Study of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Patients with Relapsed/Refractory Multiple Myeloma - ADMYRE: Aplidin - Dexamethasone in RElapsed/Refractory MYeloma
• Scientific title: Randomized, Multicenter, Open-label, Phase III Study of Plitidepsin in Combination with Dexamethasone vs. Dexamethasone Alone in Patients with Relapsed/Refractory Multiple Myeloma - ADMYRE: Aplidin - Dexamethasone in RElapsed/Refractory MYeloma
• Date of first enrolment: 20/05/2010
• Target sample size: 250
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016138-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Czech Republic, France, Germany, Greece, Ireland, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age >/= 18 years. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) /=3 months. 4. Patients previously diagnosed with multiple myeloma based on IMWG diagnostic criteria (see Appendix 4). 5. Patients must have relapsed or relapsed and refractory multiple myeloma (MM) (Appendix 5) 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. 6. Patients must have received previous bortezomib-containing and lenalidomide-containing regimens (or thalidomide where lenalidomide is not available), unless unable to tolerate either of them. 7. Patients must have measurable disease defined as: a) For secretory MM: any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion >/= 200 mg/24 hours. b) For oligo- or non-secretory MM: presence of soft tissue (not bone) plasmacytomas, as determined by clinical examination or applicable radiographs [i.e., magnetic resonance imaging (MRI), computed tomography (CT)-scan], and/or by the presence of abnormal serum free light chains (sFLC): involved FLC level >/= 10 mg/dl provided the serum FLC ratio is abnormal. 8. At least two-week washout period since the end of last therapy(six weeks if previous nitrosoureas-containing regimen), given recovery to grade /= 1.0 x 10^9/l (>/= 0.5 x 10^9/l if due to extensive and documented BM involvement by >/= 50% of plasma cells in BM biopsy). - Screening of ANC should be independent of granulocyte- and granulocyte/macrophage-colony stimulating factor (G-CSF and GM-CSF) support for at least one week and of pegylated G-CSF for at least two weeks. b) Platelet count >/= 50 x 10^9/l (>/= 25 x 10^9/l if due to extensive and documented BM disease involvement). c) Hemoglobin >/= 8.5 g/dl. - Patients may receive red blood cells (RBC) and/or erythropoietin (EPO), and/or platelets transfusions in accordance with institutional guidelines. d) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) /= 30 ml/minute (by means of Cockcroft and Gault´s formula) (see Appendix 3). g) Creatine phosphokinase (CPK) /= 2.5 g/dl. 10. Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) above the lower limit of normal (LLN). 11. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment. 12. Voluntarily signed and dated written informed consent prior to any specific study procedure
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Concomitant diseases/conditions: a) History or presence of angina, myocardial infarction, clinically relevant valvular heart disease, cardiac amyloidosis or congestive heart failure within the last 12 months. b) Symptomatic arrhythmia (excluding anemia-related sinusal tachycardia grade /= 2. c) Active uncontrolled infection or recent history of acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose. d) Morphological or cytological features of myelodysplasia and/or post-chemotherapy aplasia on BM assessment. e) Myopathy > grade 2 or any clinical situation that causes significant and persistent elevation of CPK (>2.5 x ULN in two different determinations performed one week apart). f) Known human immunodeficiency virus (HIV) infection (HIV testing is not required unless infection is clinically suspected). g) Known active hepatitis B or C virus (HBV or HCV) infection. h) Limitation of the patient`s ability to comply with the treatment or follow-up requirements. i) Any other major illness that, in the Investigator`s judgment, will substantially increase the risk associated with the patient`s participation in this study. j) Peripheral neuropathy > grade 2. 2. Women who are pregnant or breast feeding. 3. Concomitant medications that include corticosteroids,chemotherapy, or other therapy that is or may be active against MM,within two weeks prior to Cycle 1 Day 1. Concurrent corticosteroids are allowed, provided they are administered at an equivalent prednisone dose of

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsed/refractory multiple myeloma
MedDRA version: 12.1 Level: LLT Classification code 10028228 Term: Multiple myeloma

Intervention(s)

Product Name: Aplidin
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: Plitidepsin
CAS Number: 137219-37-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Trade Name: Fortecortin 4 mg Tabletten
Pharmaceutical Form: Tablet
INN or Proposed INN: Dexamethasone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Primary Outcome(s)

Main Objective: 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).

Secondary Objective: - To evaluate tumor response according to the International Myeloma Working Group (IMWG) criteria. - To assess duration of response (DR) and overall survival (OS). - To assess efficacy in patients who undergo crossover from dexamethasone alone to plitidepsin and dexamethasone combination. - To characterize and compare the safety profile on both arms in this population. - To characterize the pharmacokinetics (PK) and pharmacokinetic /pharmacodynamic (PK/PD) relationship.

Primary end point(s): Efficacy: • PFS, according to IRC assessment, as per intention-to-treat (ITT) analysis.

Secondary ID(s)

APL-C-001-09

2009-016138-29-FR

Ethics review

Status: Approved
Approval date: 20/05/2010
Contact:

Results

• Results available: Yes
• Date Posted: 18/11/2018
• Date Completed: 20/11/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-016138-29/results