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Study of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Patients With Multiple Myeloma

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: NCT02100657
Recruitment Status : Completed
First Posted : April 1, 2014
Results First Posted : October 12, 2020
Last Update Posted : October 12, 2020
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Multiple Myeloma
Interventions Drug: Plitidepsin
Drug: Bortezomib
Drug: Dexamethasone
Enrollment 39
Recruitment Details 39 patients were enrolled at 7 sites in Spain and France and 36 of them were treated with the combination of plitidepsin, bortezomib (BTZ) and dexamethasone (DXM). Patients who participated between 18Jun2014-30Aug2018 (cutoff date). The first dose of the first cycle was administered on 7Jul2014 and the last cycle was administered on 25May2018
Pre-assignment Details Age≥18;Consent Informed (CI) signed;Confirmed diagnosis of MM according to the Durie-Salmon criteria;Relapsed and/or refractory disease;Eastern Cooperative Oncology Group performance status (ECOG PS)≤2
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Period Title: Cohort 1: Dose Level 1
Started 8 0 0
Completed 0 0 0
Not Completed 8 0 0
Reason Not Completed
Progressive disease             6             0             0
Treatment-related adverse event             1             0             0
Withdrawal by Subject             1             0             0
Period Title: Cohort 2: Dose Level 2
Started 0 4 0
Completed 0 0 0
Not Completed 0 4 0
Reason Not Completed
Progressive disease             0             2             0
Physician Decision             0             1             0
Treatment-related adverse event             0             1             0
Period Title: Cohort 3: Dose Level 3
Started 0 0 27
Completed 0 0 0
Not Completed 0 0 27
Reason Not Completed
Progressive disease             0             0             15
Death             0             0             1
Non-treatment related adverse event             0             0             1
Physician Decision             0             0             1
Never were treated             0             0             3
Treatment-related adverse event             0             0             3
Withdrawal by Subject             0             0             3
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Total
Hide Arm/Group Description Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles Total of all reporting groups
Overall Number of Baseline Participants 8 4 27 39
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
2
  25.0%
2
  50.0%
14
  51.9%
18
  46.2%
>=65 years
6
  75.0%
2
  50.0%
13
  48.1%
21
  53.8%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 8 participants 4 participants 27 participants 39 participants
68
(57 to 80)
67
(58 to 76)
64
(51 to 80)
66
(51 to 80)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
Female
3
  37.5%
3
  75.0%
12
  44.4%
18
  46.2%
Male
5
  62.5%
1
  25.0%
15
  55.6%
21
  53.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
White
8
 100.0%
4
 100.0%
24
  88.9%
36
  92.3%
Black
0
   0.0%
0
   0.0%
2
   7.4%
2
   5.1%
Not reported
0
   0.0%
0
   0.0%
1
   3.7%
1
   2.6%
ECOG PS   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
PS 0
1
  12.5%
2
  50.0%
5
  18.5%
8
  20.5%
PS 1
6
  75.0%
2
  50.0%
21
  77.8%
29
  74.4%
PS 2
1
  12.5%
0
   0.0%
1
   3.7%
2
   5.1%
[1]
Measure Description: ECOG PS, Eastern Cooperative Oncology Group performance status PS 0 Fully active able to carry on all pre-disease performance without restriction PS 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature PS 2 Ambulatory and capable of all selfcare but unable to carry out any work activities up and about more than 50% of waking hours PS 3 Capable of only limited selfcare confined to bed or chair more than 50% of waking hours PS 4 Completely disabled cannot carry on any selfcare; totally confined to bed or chair PS 5 Dead
Multiple myeloma type at diagnosis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
Non-secretory
1
  12.5%
0
   0.0%
1
   3.7%
2
   5.1%
Oligosecretory
0
   0.0%
0
   0.0%
1
   3.7%
1
   2.6%
Secretory
7
  87.5%
4
 100.0%
25
  92.6%
36
  92.3%
Durie-Salmon stage at diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
Stage I
2
  25.0%
0
   0.0%
1
   3.7%
3
   7.7%
Stage II
5
  62.5%
1
  25.0%
6
  22.2%
12
  30.8%
Stage III
1
  12.5%
3
  75.0%
20
  74.1%
24
  61.5%
[1]
Measure Description:

Stage I: small number of myeloma cells. All are present:

  • Hemoglobin >100 g/L
  • Blood calcium <2.8 mmol/L
  • No areas of bone damage or a solitary plasmacytoma of the bone
  • Immunoglobulin G (IgG) <50 g/L
  • Immunoglobulin A (IgA) <30 g/L
  • Urine M-protein <4 g

Stage II: Moderate number of myeloma cells. The features are between stage 1 and 3

Stage III: Large number of myeloma cells. One/more are present:

  • Hemoglobin <85 g/L
  • Blood calcium >2.8 mmol/L
  • Several areas of bone damage
  • IgG >70 g/L
  • IgA >50 g/L
  • Urine M-protein >12 g
Durie-Salmon stage at diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
Stage I
2
  25.0%
0
   0.0%
1
   3.7%
3
   7.7%
Stage II
5
  62.5%
1
  25.0%
6
  22.2%
12
  30.8%
Stage III
1
  12.5%
3
  75.0%
20
  74.1%
24
  61.5%
[1]
Measure Description:

Stage I: small number of myeloma cells. All are present:

  • Hemoglobin more than 100 g/L
  • Blood calcium less than 2.8 mmol/L
  • No areas of bone damage or a solitary plasmacytoma of the bone
  • IgG less than 50 g/L
  • IgA less than 30 g/L
  • Urine M-protein less than 4 g

Stage II: Moderate number of myeloma cells. The features are between stage 1 and 3

Stage III: Large number of myeloma cells. One/more are present:

  • Hemoglobin less than 85 g/L
  • Blood calcium more than 2.8 mmol/L
  • Several areas of bone damage
  • IgG more than 70 g/L
  • IgA more than 50 g/L
  • Urine M-protein more than 12 g
Durie-Salmon subclassification at diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
Substage A
8
 100.0%
3
  75.0%
19
  70.4%
30
  76.9%
Substage B
0
   0.0%
1
  25.0%
8
  29.6%
9
  23.1%
[1]
Measure Description:

The stages of multiple myeloma are further divided according to creatinine level in the blood, which shows how well the kidneys are working.

Substage A: Kidney function is normal. Creatinine level is less than 180 µmol/L.

Substage B: Kidney function is abnormal. Creatinine level is 180 µmol/L or more.
International Staging System at diagnosis   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
Stage I
6
  75.0%
0
   0.0%
8
  29.6%
14
  35.9%
Stage II
0
   0.0%
1
  25.0%
5
  18.5%
6
  15.4%
Stage III
1
  12.5%
2
  50.0%
7
  25.9%
10
  25.6%
Unknown
1
  12.5%
1
  25.0%
7
  25.9%
9
  23.1%
[1]
Measure Description:

The International Staging System uses the results of 2 blood tests: albumin and beta-2-microglobulin level.

Stage 1: Beta-2-microglobulin level less than 3.5 mg/L and albumin level more equal than 35 g/L.

Stage 2: Beta-2-microglobulin level less than 3.5 mg/L and Albumin level less than 35 g/L or beta-2-microglobulin level is more than 3.5 mg/L but less than 5.5 mg/L and any albumin level.

Stage 3: Beta-2-microglobulin is 5.5 mg/L or more and any albumin level.
Disease status with respect to last prior therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
Relapsed
2
  25.0%
2
  50.0%
11
  40.7%
15
  38.5%
Total refractory
6
  75.0%
2
  50.0%
16
  59.3%
24
  61.5%
Best response to last prior anticancer therapy   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 4 participants 27 participants 39 participants
CR
0
   0.0%
1
  25.0%
1
   3.7%
2
   5.1%
VGPR
2
  25.0%
3
  75.0%
2
   7.4%
7
  17.9%
PR
3
  37.5%
0
   0.0%
9
  33.3%
12
  30.8%
SD
2
  25.0%
0
   0.0%
2
   7.4%
4
  10.3%
PD
1
  12.5%
0
   0.0%
8
  29.6%
9
  23.1%
UK
0
   0.0%
0
   0.0%
5
  18.5%
5
  12.8%
[1]
Measure Description: CR, complete response; PD, progressive disease; PR, partial response; RD, recommended dose; SD, stable disease; UK, unknown; VGPR, very good partial response.
Weight  
Median (Full Range)
Unit of measure:  Kg
Number Analyzed 8 participants 4 participants 27 participants 39 participants
70.9
(55.5 to 81.7)
65.1
(53.0 to 80.9)
72.0
(46.2 to 90.0)
70.8
(46.2 to 90.0)
Body surface area  
Median (Full Range)
Unit of measure:  M^2
Number Analyzed 8 participants 4 participants 27 participants 39 participants
1.8
(1.5 to 1.9)
1.7
(1.6 to 2.0)
1.8
(1.4 to 2.1)
1.8
(1.4 to 2.1)
Time from diagnosis to first infusion  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 8 participants 4 participants 27 participants 39 participants
65.3
(26 to 150)
55.8
(32 to 133)
64.5
(29 to 196)
64.5
(26 to 196)
Time from last progressive disease to first infusion  
Median (Full Range)
Unit of measure:  Months
Number Analyzed 8 participants 4 participants 27 participants 39 participants
1.6
(0.4 to 16.5)
5.3
(0.7 to 5.9)
1.6
(0.4 to 53.9)
1.6
(0.4 to 53.9)
Lines of prior chemotherapy  
Median (Full Range)
Unit of measure:  Lines of chemotherapy
Number Analyzed 8 participants 4 participants 27 participants 39 participants
2
(1 to 4)
2
(1 to 9)
5
(1 to 9)
4
(1 to 9)
Agents of prior chemotherapy  
Median (Full Range)
Unit of measure:  Agents of chemotherapy
Number Analyzed 8 participants 4 participants 27 participants 39 participants
6.5
(3 to 11)
5.0
(2 to 11)
8.0
(2 to 15)
7.0
(2 to 15)
1.Primary Outcome
Title Recommended Dose of Plitidepsin in Combination With Bortezomib and Dexamethasone
Hide Description To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
Time Frame After 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose study treatment
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants who received at least 1 dose of plitidepsin as a 3-hour i.v. infusion on Days 1 and 15 in combination with BTZ administered s.c. on Days 1, 4, 8 and 11, and DXM orally on Days 1, 8, 15 and 22 q4wk in patients with relapsed and/or refractory MM
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: mg/m^2 of plitidepsin
5.0
2.Primary Outcome
Title Recommended Dose of Bortezomib in Combination With Plitidepsin and Dexamethasone
Hide Description To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
Time Frame After 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose study treatment
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants who received at least 1 dose of plitidepsin as a 3-hour i.v. infusion on Days 1 and 15 in combination with BTZ administered s.c. on Days 1, 4, 8 and 11, and DXM orally on Days 1, 8, 15 and 22 q4wk in patients with relapsed and/or refractory MM
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: mg/m^2 of bortezomib
1.3
3.Primary Outcome
Title Recommended Dose of Dexamethasone in Combination With Plitidepsin and Bortezomib
Hide Description To determine the recommended dose (RD) of plitidepsin in combination with bortezomib and dexamethasone in patients with relapsed and/or refractory multiple myeloma (MM). To define the RD, patients will be evaluated for DLTs during the first 28-day cycle. The RD will be the highest DL at which fewer than two out of six (33%) of evaluable patients experience a DLT during the first 28-day cycle.
Time Frame After 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least 1 dose study treatment
Arm/Group Title All Participants
Hide Arm/Group Description:
All participants who received at least 1 dose of plitidepsin as a 3-hour i.v. infusion on Days 1 and 15 in combination with BTZ administered s.c. on Days 1, 4, 8 and 11, and DXM orally on Days 1, 8, 15 and 22 q4wk in patients with relapsed and/or refractory MM
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: mg of dexamethasone
40.0
4.Primary Outcome
Title Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Hide Description

DLTs were defined as:

Hematological Toxicity

  • Grade 3/4 neutropenia associated with fever or lasting>7 days related to the study treatment
  • Grade 3/4 thrombocytopenia accompanied by grade 3/4 hemorrhage
  • Extensive bone marrow (BM) infiltration, DLT was defined as grade 4 thrombocytopenia with grade 3/4 hemorrhage or grade 4 neutropenia lasting >7 days or with fever Non-hematological Toxicity
  • Grade 3/4 nausea and vomiting refractory to antiemetic therapy
  • Grade≥3 muscular Adverse events (AE) (myalgia, muscular weakness, muscle cramps, myopathy)
  • Grade≥3 alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) lasting more than 1 week
  • Grade≥3 bilirubin increase
  • Grade≥3 creatine phosphokinase (CPK) increase

  • Cardiac toxicity

    • Symptomatic or treatment-requiring grade ≥1 cardiac arrhythmia related to plitidepsin
    • Grade≥1 left ventricular systolic dysfunction related to plitidepsin
  • Neuropathic pain and peripheral sensory neuropathy related to BTZ
Time Frame After 28-day cycle
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 3 3 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
2
  16.7%
5.Secondary Outcome
Title Response According to International Myeloma Working Group Criteria
Hide Description Stringent complete response (sCR) normal Free Light Chains (FLC) ratio. No clonal cells Complete response (CR) no serum/urine M-protein, no evidence of soft tissue plasmacytoma. <5% clonal plasma cells 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
Time Frame Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 7 3 18
Measure Type: Count of Participants
Unit of Measure: Participants
sCR
0
   0.0%
1
  33.3%
1
   5.6%
CR
1
  14.3%
0
   0.0%
0
   0.0%
VGPR
2
  28.6%
0
   0.0%
1
   5.6%
PR
1
  14.3%
1
  33.3%
2
  11.1%
MR
1
  14.3%
1
  33.3%
1
   5.6%
SD≥4 months
1
  14.3%
0
   0.0%
2
  11.1%
SD<4 months
0
   0.0%
0
   0.0%
7
  38.9%
PD
1
  14.3%
0
   0.0%
4
  22.2%
6.Secondary Outcome
Title Overall Response Rate
Hide Description Overall response rate (ORR), including stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR) according to the International Myeloma Working Group (IMWG) criteria
Time Frame Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 7 3 18
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
57.1
(18.4 to 90.1)
66.7
(9.4 to 99.2)
22.2
(6.4 to 47.6)
7.Secondary Outcome
Title Duration of Response
Hide Description Duration of response (DR) was analyzed for all patients in whom a response had been observed and was calculated from the date of the first documentation of response to the date of PD or further therapy or death
Time Frame From the date of the first documentation of response to the date of PD or further therapy or death, up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 4 2 4
Median (95% Confidence Interval)
Unit of Measure: months
21.0
(6.5 to 26.6)
12.6
(10.8 to 14.4)
12.3
(1.8 to 23.9)
8.Secondary Outcome
Title Time to Progression
Hide Description Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.
Time Frame From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 7 3 18
Median (95% Confidence Interval)
Unit of Measure: months
10.4
(1.8 to 27.6)
13.6
(3.7 to 15.3)
2.8
(1.2 to 4.8)
9.Secondary Outcome
Title Time to Progression Rates
Hide Description Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.
Time Frame From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 7 3 18
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
At 3 months
85.7
(59.8 to 100.0)
100.0
(100.0 to 100.0)
44.4
(21.5 to 67.4)
At 6 months
71.4
(38.0 to 100.0)
66.7
(13.3 to 100.0)
26.7
(5.7 to 47.6)
At 12 months
35.7
(0.0 to 74.5)
66.7
(13.3 to 100.0)
13.3
(0.0 to 30.1)
10.Secondary Outcome
Title Progression-free Survival
Hide Description Progression-free survival (PFS) was calculated from the date of the first infusion to the date of documented PD or death (regardless of the reason), whichever comes first
Time Frame from the date of the first infusion to the date of documented PD or death, up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 7 3 18
Mean (95% Confidence Interval)
Unit of Measure: months
10.4
(1.8 to 27.6)
13.6
(3.7 to 15.3)
2.8
(1.2 to 4.8)
11.Secondary Outcome
Title Progression-free Survival Rates
Hide Description Progression-free survival (PFS) was calculated from the date of the first infusion to the date of documented PD or death (regardless of the reason), whichever comes first
Time Frame From the date of the first infusion to the date of documented PD or death, up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 7 3 18
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
At 3 months
85.7
(59.8 to 100.0)
100.0
(100.0 to 100.0)
44.4
(21.5 to 67.4)
At 6 months
71.4
(38.0 to 100.0)
66.7
(13.3 to 100.0)
26.7
(5.7 to 47.6)
At 12 months
35.7
(0.0 to 74.5)
66.7
(13.3 to 100.0)
13.3
(0.0 to 30.1)
12.Secondary Outcome
Title Event-free Survival
Hide Description Event-free survival (EFS) was calculated from the date of first infusion to the date of documented PD or death, but could include additional events besides death and PD that were considered of importance
Time Frame From the date of first infusion to the date of documented PD or death, up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 7 3 18
Median (95% Confidence Interval)
Unit of Measure: months
10.4
(1.8 to 27.6)
13.6
(3.7 to 15.3)
2.8
(1.2 to 4.8)
13.Secondary Outcome
Title Event-free Survival Rates
Hide Description Event-free survival (EFS) was calculated from the date of first infusion to the date of documented PD or death, but could include additional events besides death and PD that were considered of importance
Time Frame from the date of first infusion to the date of documented PD or death, up to 4 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description:
Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
Overall Number of Participants Analyzed 7 3 18
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
At 3 months
85.7
(59.8 to 100.0)
100.0
(100.0 to 100.0)
44.4
(21.5 to 67.4)
At 6 months
71.4
(38.0 to 100.0)
66.7
(13.3 to 100.0)
26.7
(5.7 to 47.6)
At 12 months
35.7
(0.0 to 74.5)
66.7
(13.3 to 100.0)
13.3
(0.0 to 30.1)
Time Frame Participants were assessed through study completion, approximately 4 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Hide Arm/Group Description Patients received plitidepsin 4 mg/m2 and BTZ 1 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles Patients received plitidepsin 4 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles Patients received plitidepsin 5 mg/m2 and BTZ 1.3 mg/m2 and DXM 40 mg. DXM was administered at least one hour before the start of plitidepsin infusion, and BTZ was administered one minute after the end of the plitidepsin infusion. Patients received a maximum of eight treatment cycles
All-Cause Mortality
Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/8 (12.50%)      0/4 (0.00%)      1/24 (4.17%)    
Hide Serious Adverse Events
Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/8 (62.50%)      3/4 (75.00%)      12/24 (50.00%)    
Blood and lymphatic system disorders       
anaemia † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
Cardiac disorders       
atrial fibrillation † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 1/24 (4.17%)  1
acute coronary syndrome † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
cardiac failure † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
Gastrointestinal disorders       
diarrhoea † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 2/24 (8.33%)  2
vomiting † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 1/24 (4.17%)  1
nausea † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 2/24 (8.33%)  2
Immune system disorders       
hypersensitivity † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 0/24 (0.00%)  0
Infections and infestations       
pneumonia † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 2/24 (8.33%)  2
respiratory tract infection † 1  1/8 (12.50%)  3 0/4 (0.00%)  0 2/24 (8.33%)  3
diverticulitis † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
escherichia infection † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
gastrointestinal infection † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
pneumonia pneumococcal † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  2
respiratory syncytial virus infection † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
Injury, poisoning and procedural complications       
Femur fracture † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 1/24 (4.17%)  1
Rib fracture † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
Spinal fracture † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
Metabolism and nutrition disorders       
hypercalcaemia † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
Musculoskeletal and connective tissue disorders       
bone pain † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
musculoskeletal pain † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 0/24 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
tumour pain † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 2/24 (8.33%)  2
Nervous system disorders       
spinal cord compression † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
sciatica † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
Renal and urinary disorders       
renal failure † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
Respiratory, thoracic and mediastinal disorders       
lung disorder † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 1/24 (4.17%)  1
1
Term from vocabulary, MedDRA (16.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Plitidepsin (4 mg/m2)+BTZ (1 mg/m2)+DXM (40 mg) Plitidepsin (4 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg) Plitidepsin (5 mg/m2)+BTZ (1.3 mg/m2)+DXM (40 mg)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/8 (100.00%)      4/4 (100.00%)      24/24 (100.00%)    
Blood and lymphatic system disorders       
anaemia † 1  4/8 (50.00%)  13 0/4 (0.00%)  0 10/24 (41.67%)  23
thrombocytopenia † 1  3/8 (37.50%)  9 1/4 (25.00%)  3 7/24 (29.17%)  21
neutropenia † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 3/24 (12.50%)  3
Cardiac disorders       
atrial fibrillation † 1  1/8 (12.50%)  11 2/4 (50.00%)  7 0/24 (0.00%)  0
Ear and labyrinth disorders       
vertigo † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
deafness † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 2/24 (8.33%)  4
Eye disorders       
conjunctival haemorrhage † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 0/24 (0.00%)  0
Gastrointestinal disorders       
abdominal pain upper † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
diarrhoea † 1  3/8 (37.50%)  7 2/4 (50.00%)  2 7/24 (29.17%)  27
nausea † 1  2/8 (25.00%)  8 3/4 (75.00%)  11 8/24 (33.33%)  16
vomiting † 1  1/8 (12.50%)  1 2/4 (50.00%)  4 5/24 (20.83%)  6
abdominal distension † 1  0/8 (0.00%)  0 1/4 (25.00%)  4 0/24 (0.00%)  0
constipation † 1  0/8 (0.00%)  0 1/4 (25.00%)  2 3/24 (12.50%)  6
intestinal obstruction † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 0/24 (0.00%)  0
abdominal pain † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 3/24 (12.50%)  4
General disorders       
asthenia/fatigue † 1  5/8 (62.50%)  43 3/4 (75.00%)  24 11/24 (45.83%)  62
discomfort † 1  2/8 (25.00%)  3 0/4 (0.00%)  0 0/24 (0.00%)  0
oedema peripheral † 1  3/8 (37.50%)  29 3/4 (75.00%)  10 2/24 (8.33%)  19
chest pain † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 1/24 (4.17%)  1
feeling of body temperature change † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 0/24 (0.00%)  0
injection site erythema † 1  0/8 (0.00%)  0 1/4 (25.00%)  2 0/24 (0.00%)  0
malaise † 1  0/8 (0.00%)  0 1/4 (25.00%)  2 1/24 (4.17%)  1
pyrexia † 1  0/8 (0.00%)  0 1/4 (25.00%)  4 1/24 (4.17%)  2
extravasation † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 2/24 (8.33%)  3
Infections and infestations       
bronchitis † 1  2/8 (25.00%)  5 0/4 (0.00%)  0 1/24 (4.17%)  2
cellulitis † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
gastroenteritis † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 1/24 (4.17%)  1
hordeolum † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 0/24 (0.00%)  0
lower respiratory tract infection † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
nasopharyngitis † 1  2/8 (25.00%)  4 3/4 (75.00%)  4 1/24 (4.17%)  3
pneumonia † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 2/24 (8.33%)  2
respiratory tract infection † 1  3/8 (37.50%)  5 1/4 (25.00%)  2 3/24 (12.50%)  7
upper respiratory tract infection † 1  3/8 (37.50%)  5 0/4 (0.00%)  0 0/24 (0.00%)  0
Injury, poisoning and procedural complications       
humerus fracture † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
upper limb fracture † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 0/24 (0.00%)  0
wrist fracture † 1  1/8 (12.50%)  3 0/4 (0.00%)  0 0/24 (0.00%)  0
fall † 1  0/8 (0.00%)  0 1/4 (25.00%)  3 0/24 (0.00%)  0
scapula fracture † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 0/24 (0.00%)  0
Investigations       
alanine aminotransferase increased † 1  2/8 (25.00%)  4 1/4 (25.00%)  1 10/24 (41.67%)  36
aspartate aminotransferase increased † 1  1/8 (12.50%)  1 1/4 (25.00%)  1 5/24 (20.83%)  6
weight decreased † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 3/24 (12.50%)  17
blood creatine phosphokinase increased † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 2/24 (8.33%)  4
Metabolism and nutrition disorders       
decreased appetite † 1  1/8 (12.50%)  2 1/4 (25.00%)  5 3/24 (12.50%)  7
hyperglycaemia † 1  1/8 (12.50%)  10 0/4 (0.00%)  0 0/24 (0.00%)  0
hypokalaemia † 1  3/8 (37.50%)  5 0/4 (0.00%)  0 1/24 (4.17%)  2
Musculoskeletal and connective tissue disorders       
arthralgia † 1  2/8 (25.00%)  4 0/4 (0.00%)  0 1/24 (4.17%)  1
back pain † 1  1/8 (12.50%)  3 1/4 (25.00%)  1 0/24 (0.00%)  0
bone pain † 1  2/8 (25.00%)  2 0/4 (0.00%)  0 0/24 (0.00%)  0
muscle spasms † 1  1/8 (12.50%)  2 1/4 (25.00%)  3 0/24 (0.00%)  0
myopathy † 1  1/8 (12.50%)  8 1/4 (25.00%)  1 0/24 (0.00%)  0
pain in extremity † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 1/24 (4.17%)  1
tendonitis † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
musculoskeletal chest pain † 1  0/8 (0.00%)  0 1/4 (25.00%)  2 0/24 (0.00%)  0
musculoskeletal pain † 1  0/8 (0.00%)  0 1/4 (25.00%)  2 0/24 (0.00%)  0
rotator cuff syndrome † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 0/24 (0.00%)  0
muscular weakness † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 2/24 (8.33%)  31
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
tumour pain † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 3/24 (12.50%)  5
Nervous system disorders       
aphonia † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
dizziness † 1  1/8 (12.50%)  2 1/4 (25.00%)  1 1/24 (4.17%)  1
neuropathy peripheral † 1  3/8 (37.50%)  21 2/4 (50.00%)  5 3/24 (12.50%)  11
neuralgia † 1  0/8 (0.00%)  0 1/4 (25.00%)  2 0/24 (0.00%)  0
polyneuropathy † 1  0/8 (0.00%)  0 1/4 (25.00%)  6 0/24 (0.00%)  0
syncope † 1  0/8 (0.00%)  0 1/4 (25.00%)  2 0/24 (0.00%)  0
paraesthesia † 1  0/8 (0.00%)  0 0/4 (0.00%)  0 2/24 (8.33%)  5
Psychiatric disorders       
depression † 1  1/8 (12.50%)  6 0/4 (0.00%)  0 0/24 (0.00%)  0
insomnia † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 0/24 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
cough † 1  2/8 (25.00%)  2 0/4 (0.00%)  0 0/24 (0.00%)  0
dyspnoea † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 2/24 (8.33%)  7
dyspnoea exertional † 1  1/8 (12.50%)  11 0/4 (0.00%)  0 0/24 (0.00%)  0
nasal congestion † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 1/24 (4.17%)  1
productive cough † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
respiratory failure † 1  1/8 (12.50%)  1 0/4 (0.00%)  0 0/24 (0.00%)  0
rhinorrhoea † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 0/24 (0.00%)  0
epistaxis † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 2/24 (8.33%)  3
Skin and subcutaneous tissue disorders       
erythema † 1  2/8 (25.00%)  8 0/4 (0.00%)  0 1/24 (4.17%)  1
rash † 1  1/8 (12.50%)  2 0/4 (0.00%)  0 2/24 (8.33%)  2
skin lesion † 1  1/8 (12.50%)  1 1/4 (25.00%)  1 0/24 (0.00%)  0
Surgical and medical procedures       
cataract operation † 1  0/8 (0.00%)  0 1/4 (25.00%)  2 0/24 (0.00%)  0
Vascular disorders       
Hypotension † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 0/24 (0.00%)  0
phlebitis † 1  0/8 (0.00%)  0 1/4 (25.00%)  1 1/24 (4.17%)  1
1
Term from vocabulary, MedDRA (16.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pharma Mar S.A.
Organization: Pharma Mar S.A.
Phone: 00 34 91846 60 00
EMail: clinicaltrials@pharmamar.com
Layout table for additonal information
Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT02100657    
Other Study ID Numbers: APL-A-012-13
First Submitted: March 21, 2014
First Posted: April 1, 2014
Results First Submitted: July 22, 2020
Results First Posted: October 12, 2020
Last Update Posted: October 12, 2020