Study of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Patients With Multiple Myeloma
Sponsor
PharmaMar (Industry)
Overall Status
Completed
CT.gov ID
NCT02100657
Collaborator
(none)
39
7
1
48
5.6
0.1
Study Details
Study Description
Brief Summary
Study of Plitidepsin (Aplidin®) to determine the recommended dose (RD) of plitidepsin in Combination with Bortezomib and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
Phase I Multicenter, Open-label, Dose-escalating Clinical and Pharmacokinetic Trial of Plitidepsin (Aplidin®) 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 determine the efficacy of the combination plitidepsin/bortezomib/dexamethasone, to evaluate the safety and tolerability of the combination in patients with relapsing and/or refractory MM and to study the pharmacokinetics (PK) and pharmacodynamics (PDy) of plitidepsin in combination with bortezomib and dexamethasone.
Study Design
Study Type:
Interventional
Actual Enrollment
:
39 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
Phase I Study of Plitidepsin (Aplidin®) in Combination With Bortezomib and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma
Study Start Date
:
Jun 1, 2014
Actual Primary Completion Date
:
Jun 1, 2018
Actual Study Completion Date
:
Jun 1, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: plitidepsin + bortezomib + dexamethasone Plitidepsin will be administered as a 3-hour (h) intravenous (i.v.) infusion on Day (D) 1 and 15, every four weeks (q4wk). Bortezomib will be administered as a subcutaneous (s.c.) injection on D1, 4, 8 and 11, q4wk, for a maximum of eight cycles. Dexamethasone will be taken orally on D1, 8, 15 and 22, q4wk |
Drug: Plitidepsin
Drug: Bortezomib
Drug: Dexamethasone
|
Outcome Measures
Primary Outcome Measures
- Recommended Dose of Plitidepsin in Combination With Bortezomib and Dexamethasone [After 28-day cycle]
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.
- Recommended Dose of Bortezomib in Combination With Plitidepsin and Dexamethasone [After 28-day cycle]
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.
- Recommended Dose of Dexamethasone in Combination With Plitidepsin and Bortezomib [After 28-day cycle]
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.
- Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) [After 28-day cycle]
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
Secondary Outcome Measures
- Response According to International Myeloma Working Group Criteria [Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years]
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
- Overall Response Rate [Response or disease progression was assessed on Day 1 of each cycle, assessed up to 4 years]
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
- Duration of Response [From the date of the first documentation of response to the date of PD or further therapy or death, up to 4 years]
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 to Progression [From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years]
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 to Progression Rates [From the date of the first infusion to the date of documented PD or death due to PD, up to 4 years]
Time to progression (TTP) was calculated from the date of the first infusion to the date of documented PD or death due to PD.
- Progression-free Survival [from the date of the first infusion to the date of documented PD or death, up to 4 years]
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
- Progression-free Survival Rates [From the date of the first infusion to the date of documented PD or death, up to 4 years]
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
- Event-free Survival [From the date of first infusion to the date of documented PD or death, up to 4 years]
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
- Event-free Survival Rates [from the date of first infusion to the date of documented PD or death, up to 4 years]
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
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age ≥ 18 years.
-
Prior autologous transplantation (HSCT) patients are allowed.
-
Patients must have received at least one previous treatment line of induction, chemotherapy, chemotherapy and transplantation or previous treatment with bortezomib or another proteasome drug
Exclusion Criteria:
-
Previous treatment with plitidepsin.
-
Active or metastatic primary malignancy other than MM.
-
Serious concomitant systemic disorders
-
History of hypersensitivity reactions to bortezomib, polyoxyl 35 castor oil or mannitol
-
Neuropathy
-
Pregnant and/or lactating women
-
HIV infection
-
Active hepatitis B or C virus infection.
-
Treatment with any Investigational Medicinal Product (IMP) in the 30 days before inclusion in the study
-
Plasma cell leukemia at the time of study entry
-
Contraindication for the use of steroids
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Institut Gustave Roussy | Villejuif | France | 94805 | |
| 2 | Hospital Universitario Germans Trias I Pujol | Badalona | Barcelona | Spain | 08916 |
| 3 | Clínica Universidad de Navarra | Pamplona | Navarra | Spain | 31008 |
| 4 | MD Anderson Cancer Center Madrid | Madrid | Spain | 28033 | |
| 5 | Hospital Universitario Salamanca | Salamanca | Spain | 37007 | |
| 6 | Hospital Universitario Virgen del Rocío | Sevilla | Spain | 41013 | |
| 7 | Hospital Universitari i Politècnic la Fe | Valencia | Spain | 46026 |
Sponsors and Collaborators
- PharmaMar
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
PharmaMar
ClinicalTrials.gov Identifier:
NCT02100657
Other Study ID Numbers:
- APL-A-012-13
First Posted:
Apr 1, 2014
Last Update Posted:
Oct 12, 2020
Last Verified:
Sep 1, 2020
Keywords provided by PharmaMar
Additional relevant MeSH terms:
Study Results
Participant Flow
| 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 Detail | 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) |
|---|---|---|---|
| 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 |
| Period Title: Cohort 1: Dose Level 1 | |||
| STARTED | 0 | 4 | 0 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 4 | 0 |
| Period Title: Cohort 1: Dose Level 1 | |||
| STARTED | 0 | 0 | 27 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 27 |
Baseline Characteristics
| 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 |
|---|---|---|---|---|
| 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 Participants | 8 | 4 | 27 | 39 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
2
25%
|
2
50%
|
14
51.9%
|
18
46.2%
|
| >=65 years |
6
75%
|
2
50%
|
13
48.1%
|
21
53.8%
|
| Age (years) [Median (Full Range) ] | ||||
| Median (Full Range) [years] |
68
|
67
|
64
|
66
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
3
37.5%
|
3
75%
|
12
44.4%
|
18
46.2%
|
| Male |
5
62.5%
|
1
25%
|
15
55.6%
|
21
53.8%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| White |
8
100%
|
4
100%
|
24
88.9%
|
36
92.3%
|
| Black |
0
0%
|
0
0%
|
2
7.4%
|
2
5.1%
|
| Not reported |
0
0%
|
0
0%
|
1
3.7%
|
1
2.6%
|
| ECOG PS (Count of Participants) | ||||
| PS 0 |
1
12.5%
|
2
50%
|
5
18.5%
|
8
20.5%
|
| PS 1 |
6
75%
|
2
50%
|
21
77.8%
|
29
74.4%
|
| PS 2 |
1
12.5%
|
0
0%
|
1
3.7%
|
2
5.1%
|
| Multiple myeloma type at diagnosis (Count of Participants) | ||||
| Non-secretory |
1
12.5%
|
0
0%
|
1
3.7%
|
2
5.1%
|
| Oligosecretory |
0
0%
|
0
0%
|
1
3.7%
|
1
2.6%
|
| Secretory |
7
87.5%
|
4
100%
|
25
92.6%
|
36
92.3%
|
| Durie-Salmon stage at diagnosis (Count of Participants) | ||||
| Stage I |
2
25%
|
0
0%
|
1
3.7%
|
3
7.7%
|
| Stage II |
5
62.5%
|
1
25%
|
6
22.2%
|
12
30.8%
|
| Stage III |
1
12.5%
|
3
75%
|
20
74.1%
|
24
61.5%
|
| Durie-Salmon stage at diagnosis (Count of Participants) | ||||
| Stage I |
2
25%
|
0
0%
|
1
3.7%
|
3
7.7%
|
| Stage II |
5
62.5%
|
1
25%
|
6
22.2%
|
12
30.8%
|
| Stage III |
1
12.5%
|
3
75%
|
20
74.1%
|
24
61.5%
|
| Durie-Salmon subclassification at diagnosis (Count of Participants) | ||||
| Substage A |
8
100%
|
3
75%
|
19
70.4%
|
30
76.9%
|
| Substage B |
0
0%
|
1
25%
|
8
29.6%
|
9
23.1%
|
| International Staging System at diagnosis (Count of Participants) | ||||
| Stage I |
6
75%
|
0
0%
|
8
29.6%
|
14
35.9%
|
| Stage II |
0
0%
|
1
25%
|
5
18.5%
|
6
15.4%
|
| Stage III |
1
12.5%
|
2
50%
|
7
25.9%
|
10
25.6%
|
| Unknown |
1
12.5%
|
1
25%
|
7
25.9%
|
9
23.1%
|
| Disease status with respect to last prior therapy (Count of Participants) | ||||
| Relapsed |
2
25%
|
2
50%
|
11
40.7%
|
15
38.5%
|
| Total refractory |
6
75%
|
2
50%
|
16
59.3%
|
24
61.5%
|
| Best response to last prior anticancer therapy (Count of Participants) | ||||
| CR |
0
0%
|
1
25%
|
1
3.7%
|
2
5.1%
|
| VGPR |
2
25%
|
3
75%
|
2
7.4%
|
7
17.9%
|
| PR |
3
37.5%
|
0
0%
|
9
33.3%
|
12
30.8%
|
| SD |
2
25%
|
0
0%
|
2
7.4%
|
4
10.3%
|
| PD |
1
12.5%
|
0
0%
|
8
29.6%
|
9
23.1%
|
| UK |
0
0%
|
0
0%
|
5
18.5%
|
5
12.8%
|
| Weight (Kg) [Median (Full Range) ] | ||||
| Median (Full Range) [Kg] |
70.9
|
65.1
|
72.0
|
70.8
|
| Body surface area (m^2) [Median (Full Range) ] | ||||
| Median (Full Range) [m^2] |
1.8
|
1.7
|
1.8
|
1.8
|
| Time from diagnosis to first infusion (months) [Median (Full Range) ] | ||||
| Median (Full Range) [months] |
65.3
|
55.8
|
64.5
|
64.5
|
| Time from last progressive disease to first infusion (months) [Median (Full Range) ] | ||||
| Median (Full Range) [months] |
1.6
|
5.3
|
1.6
|
1.6
|
| Lines of prior chemotherapy (lines of chemotherapy) [Median (Full Range) ] | ||||
| Median (Full Range) [lines of chemotherapy] |
2
|
2
|
5
|
4
|
| Agents of prior chemotherapy (Agents of chemotherapy) [Median (Full Range) ] | ||||
| Median (Full Range) [Agents of chemotherapy] |
6.5
|
5.0
|
8.0
|
7.0
|
Outcome Measures
| Title | Recommended Dose of Plitidepsin in Combination With Bortezomib and Dexamethasone |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose study treatment |
| Arm/Group Title | All Participants |
|---|---|
| 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 |
| Measure Participants | 18 |
| Number [mg/m^2 of plitidepsin] |
5.0
|
| Title | Recommended Dose of Bortezomib in Combination With Plitidepsin and Dexamethasone |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose study treatment |
| Arm/Group Title | All Participants |
|---|---|
| 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 |
| Measure Participants | 18 |
| Number [mg/m^2 of bortezomib] |
1.3
|
| Title | Recommended Dose of Dexamethasone in Combination With Plitidepsin and Bortezomib |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose study treatment |
| Arm/Group Title | All Participants |
|---|---|
| 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 |
| Measure Participants | 18 |
| Number [mg of dexamethasone] |
40.0
|
| Title | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 3 | 3 | 12 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
2
7.4%
|
| Title | Response According to International Myeloma Working Group Criteria |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 7 | 3 | 18 |
| sCR |
0
0%
|
1
25%
|
1
3.7%
|
| CR |
1
12.5%
|
0
0%
|
0
0%
|
| VGPR |
2
25%
|
0
0%
|
1
3.7%
|
| PR |
1
12.5%
|
1
25%
|
2
7.4%
|
| MR |
1
12.5%
|
1
25%
|
1
3.7%
|
| SD≥4 months |
1
12.5%
|
0
0%
|
2
7.4%
|
| SD<4 months |
0
0%
|
0
0%
|
7
25.9%
|
| PD |
1
12.5%
|
0
0%
|
4
14.8%
|
| Title | Overall Response Rate |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 7 | 3 | 18 |
| Mean (95% Confidence Interval) [percentage of participants] |
57.1
713.8%
|
66.7
1667.5%
|
22.2
82.2%
|
| Title | Duration of Response |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 4 | 2 | 4 |
| Median (95% Confidence Interval) [months] |
21.0
|
12.6
|
12.3
|
| Title | Time to Progression |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 7 | 3 | 18 |
| Median (95% Confidence Interval) [months] |
10.4
|
13.6
|
2.8
|
| Title | Time to Progression Rates |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 7 | 3 | 18 |
| At 3 months |
85.7
1071.3%
|
100.0
2500%
|
44.4
164.4%
|
| At 6 months |
71.4
892.5%
|
66.7
1667.5%
|
26.7
98.9%
|
| At 12 months |
35.7
446.3%
|
66.7
1667.5%
|
13.3
49.3%
|
| Title | Progression-free Survival |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 7 | 3 | 18 |
| Mean (95% Confidence Interval) [months] |
10.4
|
13.6
|
2.8
|
| Title | Progression-free Survival Rates |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 7 | 3 | 18 |
| At 3 months |
85.7
1071.3%
|
100.0
2500%
|
44.4
164.4%
|
| At 6 months |
71.4
892.5%
|
66.7
1667.5%
|
26.7
98.9%
|
| At 12 months |
35.7
446.3%
|
66.7
1667.5%
|
13.3
49.3%
|
| Title | Event-free Survival |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 7 | 3 | 18 |
| Median (95% Confidence Interval) [months] |
10.4
|
13.6
|
2.8
|
| Title | Event-free Survival Rates |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|---|
| 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 |
| Measure Participants | 7 | 3 | 18 |
| At 3 months |
85.7
1071.3%
|
100.0
2500%
|
44.4
164.4%
|
| At 6 months |
71.4
892.5%
|
66.7
1667.5%
|
26.7
98.9%
|
| At 12 months |
35.7
446.3%
|
66.7
1667.5%
|
13.3
49.3%
|
Adverse Events
| Time Frame | Participants were assessed through study completion, approximately 4 years | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| 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) | |||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/8 (12.5%) | 0/4 (0%) | 1/24 (4.2%) | |||
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 (62.5%) | 3/4 (75%) | 12/24 (50%) | |||
| Blood and lymphatic system disorders | ||||||
| anaemia | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| Cardiac disorders | ||||||
| atrial fibrillation | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| acute coronary syndrome | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| cardiac failure | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| Gastrointestinal disorders | ||||||
| diarrhoea | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 2/24 (8.3%) | 2 |
| vomiting | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 1/24 (4.2%) | 1 |
| nausea | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 |
| Immune system disorders | ||||||
| hypersensitivity | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| Infections and infestations | ||||||
| pneumonia | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 |
| respiratory tract infection | 1/8 (12.5%) | 3 | 0/4 (0%) | 0 | 2/24 (8.3%) | 3 |
| diverticulitis | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| escherichia infection | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| gastrointestinal infection | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| pneumonia pneumococcal | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 2 |
| respiratory syncytial virus infection | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| Injury, poisoning and procedural complications | ||||||
| Femur fracture | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| Rib fracture | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| Spinal fracture | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| hypercalcaemia | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||
| bone pain | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| musculoskeletal pain | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| tumour pain | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 |
| Nervous system disorders | ||||||
| spinal cord compression | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| sciatica | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| Renal and urinary disorders | ||||||
| renal failure | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| lung disorder | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
Other (Not Including 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 | 8/8 (100%) | 4/4 (100%) | 24/24 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| anaemia | 4/8 (50%) | 13 | 0/4 (0%) | 0 | 10/24 (41.7%) | 23 |
| thrombocytopenia | 3/8 (37.5%) | 9 | 1/4 (25%) | 3 | 7/24 (29.2%) | 21 |
| neutropenia | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 3/24 (12.5%) | 3 |
| Cardiac disorders | ||||||
| atrial fibrillation | 1/8 (12.5%) | 11 | 2/4 (50%) | 7 | 0/24 (0%) | 0 |
| Ear and labyrinth disorders | ||||||
| vertigo | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| deafness | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 2/24 (8.3%) | 4 |
| Eye disorders | ||||||
| conjunctival haemorrhage | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| abdominal pain upper | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| diarrhoea | 3/8 (37.5%) | 7 | 2/4 (50%) | 2 | 7/24 (29.2%) | 27 |
| nausea | 2/8 (25%) | 8 | 3/4 (75%) | 11 | 8/24 (33.3%) | 16 |
| vomiting | 1/8 (12.5%) | 1 | 2/4 (50%) | 4 | 5/24 (20.8%) | 6 |
| abdominal distension | 0/8 (0%) | 0 | 1/4 (25%) | 4 | 0/24 (0%) | 0 |
| constipation | 0/8 (0%) | 0 | 1/4 (25%) | 2 | 3/24 (12.5%) | 6 |
| intestinal obstruction | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| abdominal pain | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 3/24 (12.5%) | 4 |
| General disorders | ||||||
| asthenia/fatigue | 5/8 (62.5%) | 43 | 3/4 (75%) | 24 | 11/24 (45.8%) | 62 |
| discomfort | 2/8 (25%) | 3 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| oedema peripheral | 3/8 (37.5%) | 29 | 3/4 (75%) | 10 | 2/24 (8.3%) | 19 |
| chest pain | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 1/24 (4.2%) | 1 |
| feeling of body temperature change | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| injection site erythema | 0/8 (0%) | 0 | 1/4 (25%) | 2 | 0/24 (0%) | 0 |
| malaise | 0/8 (0%) | 0 | 1/4 (25%) | 2 | 1/24 (4.2%) | 1 |
| pyrexia | 0/8 (0%) | 0 | 1/4 (25%) | 4 | 1/24 (4.2%) | 2 |
| extravasation | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 2/24 (8.3%) | 3 |
| Infections and infestations | ||||||
| bronchitis | 2/8 (25%) | 5 | 0/4 (0%) | 0 | 1/24 (4.2%) | 2 |
| cellulitis | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| gastroenteritis | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| hordeolum | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| lower respiratory tract infection | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| nasopharyngitis | 2/8 (25%) | 4 | 3/4 (75%) | 4 | 1/24 (4.2%) | 3 |
| pneumonia | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 |
| respiratory tract infection | 3/8 (37.5%) | 5 | 1/4 (25%) | 2 | 3/24 (12.5%) | 7 |
| upper respiratory tract infection | 3/8 (37.5%) | 5 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| humerus fracture | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| upper limb fracture | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| wrist fracture | 1/8 (12.5%) | 3 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| fall | 0/8 (0%) | 0 | 1/4 (25%) | 3 | 0/24 (0%) | 0 |
| scapula fracture | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| Investigations | ||||||
| alanine aminotransferase increased | 2/8 (25%) | 4 | 1/4 (25%) | 1 | 10/24 (41.7%) | 36 |
| aspartate aminotransferase increased | 1/8 (12.5%) | 1 | 1/4 (25%) | 1 | 5/24 (20.8%) | 6 |
| weight decreased | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 3/24 (12.5%) | 17 |
| blood creatine phosphokinase increased | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 2/24 (8.3%) | 4 |
| Metabolism and nutrition disorders | ||||||
| decreased appetite | 1/8 (12.5%) | 2 | 1/4 (25%) | 5 | 3/24 (12.5%) | 7 |
| hyperglycaemia | 1/8 (12.5%) | 10 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| hypokalaemia | 3/8 (37.5%) | 5 | 0/4 (0%) | 0 | 1/24 (4.2%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||||
| arthralgia | 2/8 (25%) | 4 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| back pain | 1/8 (12.5%) | 3 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| bone pain | 2/8 (25%) | 2 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| muscle spasms | 1/8 (12.5%) | 2 | 1/4 (25%) | 3 | 0/24 (0%) | 0 |
| myopathy | 1/8 (12.5%) | 8 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| pain in extremity | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| tendonitis | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| musculoskeletal chest pain | 0/8 (0%) | 0 | 1/4 (25%) | 2 | 0/24 (0%) | 0 |
| musculoskeletal pain | 0/8 (0%) | 0 | 1/4 (25%) | 2 | 0/24 (0%) | 0 |
| rotator cuff syndrome | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| muscular weakness | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 2/24 (8.3%) | 31 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| tumour pain | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 3/24 (12.5%) | 5 |
| Nervous system disorders | ||||||
| aphonia | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| dizziness | 1/8 (12.5%) | 2 | 1/4 (25%) | 1 | 1/24 (4.2%) | 1 |
| neuropathy peripheral | 3/8 (37.5%) | 21 | 2/4 (50%) | 5 | 3/24 (12.5%) | 11 |
| neuralgia | 0/8 (0%) | 0 | 1/4 (25%) | 2 | 0/24 (0%) | 0 |
| polyneuropathy | 0/8 (0%) | 0 | 1/4 (25%) | 6 | 0/24 (0%) | 0 |
| syncope | 0/8 (0%) | 0 | 1/4 (25%) | 2 | 0/24 (0%) | 0 |
| paraesthesia | 0/8 (0%) | 0 | 0/4 (0%) | 0 | 2/24 (8.3%) | 5 |
| Psychiatric disorders | ||||||
| depression | 1/8 (12.5%) | 6 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| insomnia | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| cough | 2/8 (25%) | 2 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| dyspnoea | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 2/24 (8.3%) | 7 |
| dyspnoea exertional | 1/8 (12.5%) | 11 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| nasal congestion | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| productive cough | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| respiratory failure | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| rhinorrhoea | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 0/24 (0%) | 0 |
| epistaxis | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 2/24 (8.3%) | 3 |
| Skin and subcutaneous tissue disorders | ||||||
| erythema | 2/8 (25%) | 8 | 0/4 (0%) | 0 | 1/24 (4.2%) | 1 |
| rash | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 | 2/24 (8.3%) | 2 |
| skin lesion | 1/8 (12.5%) | 1 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| Surgical and medical procedures | ||||||
| cataract operation | 0/8 (0%) | 0 | 1/4 (25%) | 2 | 0/24 (0%) | 0 |
| Vascular disorders | ||||||
| Hypotension | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 0/24 (0%) | 0 |
| phlebitis | 0/8 (0%) | 0 | 1/4 (25%) | 1 | 1/24 (4.2%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Pharma Mar S.A. |
|---|---|
| Organization | Pharma Mar S.A. |
| Phone | 00 34 91846 60 00 |
| clinicaltrials@pharmamar.com |
Responsible Party:
PharmaMar
ClinicalTrials.gov Identifier:
NCT02100657
Other Study ID Numbers:
- APL-A-012-13
First Posted:
Apr 1, 2014
Last Update Posted:
Oct 12, 2020
Last Verified:
Sep 1, 2020