A Study of Aplidin (Plitidepsin) 3 h iv in Subjects With Relapsing or Refractory Multiple Myeloma
Study Details
Study Description
Brief Summary
This is a phase II study to determine the efficacy following treatment with Aplidin® 5 mg/m2, given as a 3 hours intravenous infusion every 2 weeks, in patients with relapsed or refractory multiple myeloma (MM).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This is a phase II study to determine the efficacy following treatment with Aplidin® 5 mg/m2, given as a 3 h iv infusion every 2 weeks, in patients with relapsed or refractory multiple myeloma (MM) and to obtain the following :
-
Additional pharmacokinetic information for Aplidin® given as 3-hour IV infusion every 2 weeks in patients with MM.
-
To obtain additional genomic and pharmacodynamics information on MM and Aplidin.
-
To assess the safety and tolerability of Aplidin® given as 3-hour IV infusion every 2 weeks in patients with MM alone or in combination with dexamethasone given orally as a 20 mg daily for 4 days
-
To determine the response rate in the second cohort of patients following treatment with Aplidin®, given as a 3 hour infusion every 2 weeks, plus dexamethasone given orally as a 20 mg daily for 4 days, starting the same day of Aplidin® administration, as a second treatment stage in patients with suboptimal response to Aplidin® as single agent (progressive disease after three cycles or stable disease after four cycles).
Study Design
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR), Defined as the Combined Rate of Complete Response, Partial Response and Minimal Response [Every 2 weeks until progression or death occurs.]
Complete response(CR):0 percentage the original monoclonal protein level from blood and urine Partial response(PR): ≥50 percentage reduction in the level of serum monoclonal protein Minimal response(MR):≥25 percentage to ≤ 49 percentage reduction in the level of serum monoclonal protein Stable disease: Not meeting the criteria for MR or PD. Progressive disease: >25 percentage increase in level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation. Treatmen failure: Reappearance of serum or urinary paraprotein
Secondary Outcome Measures
- Time to Progression (TTP) [Every 2 weeks until progression or death due to progression occurs. Median TTP and TTP rates at 3 months and 6 months were assessed.]
Time to Progression (TTP):date of first infusion to the date of documented progressive disease which can be defined as >25 percentage increase in level of serum monoclonal paraprotein.
- Progression Free Survival (PFS) [Every 2 weeks until progression or death occurs. Median PFS and PFS rates at 3 months and 6 months were assessed.]
Progression Free Survival (PFS): time from the date of first infusion to the date of documented progression or death
- Number of Patients With Overall Survival (OS) [Start of treatment to death. At each patient visit while on treatment, then every 3m during follow-up. Median OS and OS rates at 6 months and 12 months were assessed.]
Overall Survival (OS): time from the date of first infusion to the date of documented death
Eligibility Criteria
Criteria
Inclusion criteria
-
Written informed consent obtained from the patient before starting any study-specific procedure. If any patient is unable to give consent, it may be obtained from the patient's legal representative if in accordance with local laws and regulations
-
Age ≥ 18 years
-
Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2
-
Life expectancy ≥ 3 months.
-
Patient was previously diagnosed with MM based on standard criteria and currently requires treatment because MM relapses following a response to standard chemotherapy or high-dose chemotherapy, or MM is refractory (i.e., failure to achieve at least complete response (CR), partial response (PR) or stable disease (SD)) to their most recent chemotherapy.
-
Patient has measurable disease, defined as follows:
-
For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion of ≥ 200 mg/24 hours.
-
For oligo or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. Magnetic resonance imaging (MRI), Computerized Axial Tomography (CT-Scan)).
-
Recovery from any non-hematological toxicity derived from previous treatments. The presence of alopecia and National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade < 2 sensitive peripheral neuropathy is allowed.
-
Patient has the following laboratory values within 14 days before day 1, cycle 1:
-
Platelet count ≥ 50 x109/L, hemoglobin ≥ 8.0 g/dl and absolute neutrophil count (ANC) ≥ 1.0x109/L; lower values may be accepted if clearly are due to bone marrow involvement by multiple myeloma.
-
Corrected serum calcium < 14mg/dL.
-
Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.
-
Alanine transaminase (ALT): ≤ 2.5 x the upper limit of normal.
-
Total bilirubin: ≤ 1.5 x the upper limit of normal.
-
Calculated Creatinine clearance: ≥ 40 mL/minute (by means of Crockoft and Gault´s formula).
- Left ventricular ejection fraction within normal limits.
Exclusion criteria
-
Prior therapy with Aplidin®.
-
Pregnant or lactating women; men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception)
-
History of another neoplastic disease. The exceptions are:
-
non-melanoma skin cancer,
-
carcinoma in situ of uterine cervix,
-
any other cancer curatively treated and no evidence of disease for at least 10 years.
- Other relevant diseases or adverse clinical conditions:
-
History or presence of unstable angina, myocardial infarction, valvular heart disease or congestive heart failure.
-
Previous mediastinal radiotherapy.
-
Uncontrolled arterial hypertension despite optimal medical therapy.
-
Previous treatment with doxorubicin at cumulative doses in excess of 400 mg/m².
-
Symptomatic arrhythmia or any arrhythmia requiring treatment.
-
History of significant neurological or psychiatric disorders
-
Active infection
-
Patient is known to be human immunodeficiency virus (HIV) positive, Hepatitis B surface antigen-positive or active hepatitis C infection.
-
Myopathy or any clinical situation that causes significant and persistent elevation of creatine kinase (CK)(>2.5 ULN in two different determinations performed with one week apart)
-
Significant non-neoplastic liver disease (e.g. cirrhosis, active chronic hepatitis)
-
Uncontrolled endocrine diseases (e.g. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months)
-
Limitation of the patient's ability to comply with the treatment or follow-up protocol.
-
Treatment with any investigational product in the 30 days period before inclusion in the study or radiotherapy in the 4 weeks before inclusion in the study. Other previous treatments should have been completed 3 weeks before inclusion in the study, and in case of high dose chemotherapy, 8 weeks.
-
Known hypersensitivity to Aplidin®, mannitol, cremophor, or ethanol or dexamethasone.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Jerome Lipper Multiple Myeloma Center - Dept of Medical Oncology - Dana Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
Sponsors and Collaborators
- PharmaMar
Investigators
- Study Chair: Paul Richardson, MD, Chief division hematological malignancies - Medical Oncology - Dana Farber Cancer Institute - Harvard Medical School, Boston
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APL-B-014-03
Study Results
Participant Flow
| Recruitment Details | Patients were recruited in 10 centers in Spain and USA between June 2004 and June 2008. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Plitidepsin | Plitidepsin + Dexamethasone |
|---|---|---|
| Arm/Group Description | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks. | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks plus 20 mg of oral dexamethasone every day on days 1 to 4 of each cycle, starting at the same time than the plitidepsin infusion. |
| Period Title: Overall Study | ||
| STARTED | 32 | 19 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 32 | 19 |
Baseline Characteristics
| Arm/Group Title | Plitidepsin | Plitidepsin + Dexamethasone | Total |
|---|---|---|---|
| Arm/Group Description | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks. | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks plus 20 mg of oral dexamethasone every day on days 1 to 4 of each cycle, starting at the same time than the plitidepsin infusion. | Total of all reporting groups |
| Overall Participants | 32 | 19 | 51 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
66
|
63
|
64.0
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
15
46.9%
|
6
31.6%
|
21
41.2%
|
| Male |
17
53.1%
|
13
68.4%
|
30
58.8%
|
| ECOG PS (patients) [Number] | |||
| 0 Units of Scale |
6
|
6
|
12
|
| 1 Units of Scale |
18
|
9
|
27
|
| 2 Units of Scale |
8
|
4
|
12
|
Outcome Measures
| Title | Objective Response Rate (ORR), Defined as the Combined Rate of Complete Response, Partial Response and Minimal Response |
|---|---|
| Description | Complete response(CR):0 percentage the original monoclonal protein level from blood and urine Partial response(PR): ≥50 percentage reduction in the level of serum monoclonal protein Minimal response(MR):≥25 percentage to ≤ 49 percentage reduction in the level of serum monoclonal protein Stable disease: Not meeting the criteria for MR or PD. Progressive disease: >25 percentage increase in level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation. Treatmen failure: Reappearance of serum or urinary paraprotein |
| Time Frame | Every 2 weeks until progression or death occurs. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol - Only 29 of 32 and 18 of 19 enrolled patients were evaluable (analyzed patients) |
| Arm/Group Title | Plitidepsin | Plitidepsin + Dexamethasone |
|---|---|---|
| Arm/Group Description | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks. | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks plus 20 mg of oral dexamethasone every day on days 1 to 4 of each cycle, starting at the same time than the plitidepsin infusion. |
| Measure Participants | 29 | 18 |
| Complete response |
0
|
0
|
| Partial response |
3
|
11
|
| Minimal response |
7
|
11
|
| Stable Disease/No changes |
41
|
61
|
| Progressive Disease/Treatment failure |
48
|
17
|
| Title | Time to Progression (TTP) |
|---|---|
| Description | Time to Progression (TTP):date of first infusion to the date of documented progressive disease which can be defined as >25 percentage increase in level of serum monoclonal paraprotein. |
| Time Frame | Every 2 weeks until progression or death due to progression occurs. Median TTP and TTP rates at 3 months and 6 months were assessed. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol - Only 29 of 32 and 18 of 19 enrolled patients were evaluable (analyzed patients) |
| Arm/Group Title | Plitidepsin | Plitidepsin + Dexamethasone |
|---|---|---|
| Arm/Group Description | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks. | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks plus 20 mg of oral dexamethasone every day on days 1 to 4 of each cycle, starting at the same time than the plitidepsin infusion. |
| Measure Participants | 29 | 18 |
| Median (Full Range) [months] |
2.3
|
4.2
|
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | Progression Free Survival (PFS): time from the date of first infusion to the date of documented progression or death |
| Time Frame | Every 2 weeks until progression or death occurs. Median PFS and PFS rates at 3 months and 6 months were assessed. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol - Only 21 of 32 and 8 of 19 enrolled patients were evaluable (analyzed patients) |
| Arm/Group Title | Plitidepsin | Plitidepsin + Dexamethasone |
|---|---|---|
| Arm/Group Description | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks. | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks plus 20 mg of oral dexamethasone every day on days 1 to 4 of each cycle, starting at the same time than the plitidepsin infusion. |
| Measure Participants | 21 | 8 |
| Median (Full Range) [months] |
2.3
|
3.8
|
| Title | Number of Patients With Overall Survival (OS) |
|---|---|
| Description | Overall Survival (OS): time from the date of first infusion to the date of documented death |
| Time Frame | Start of treatment to death. At each patient visit while on treatment, then every 3m during follow-up. Median OS and OS rates at 6 months and 12 months were assessed. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol - Only 21 of 32 and 8 of 19 enrolled patients were evaluable (analyzed patients. For patient of group plitidepsin + dexamethasone the median overall survival could not be calculated due to follow-up short duration. The survival rates at 6 and 12 months are provided instead. |
| Arm/Group Title | Plitidepsin | Plitidepsin + Dexamethasone |
|---|---|---|
| Arm/Group Description | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks. | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks plus 20 mg of oral dexamethasone every day on days 1 to 4 of each cycle, starting at the same time than the plitidepsin infusion. |
| Measure Participants | 21 | 8 |
| OS at 6 months |
70
|
76
|
| OS at 12 months |
53
|
61
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | 32 patients were treated with plitidepsin as single agent;afterwards 19 of them were treated with plitidepsin+dexamethasone combination.Therefore 32+19=51 is the no. patients at risk for plitidepsin and 19 is no. of patients at risk for dexamethasone | |||
| Arm/Group Title | Plitidepsin | Plitidepsin + Dexamethasone | ||
| Arm/Group Description | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks. | Plitidepsin 5 mg/m2 given as a 3-hour i.v. infusion every two weeks plus 20 mg of oral dexamethasone every day on days 1 to 4 of each cycle, starting at the same time than the plitidepsin infusion. | ||
All Cause Mortality |
||||
| Plitidepsin | Plitidepsin + Dexamethasone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Plitidepsin | Plitidepsin + Dexamethasone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 32/51 (62.7%) | 11/19 (57.9%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 1/51 (2%) | 0/19 (0%) | ||
| Atrial flutter | 0/51 (0%) | 1/19 (5.3%) | ||
| Cardiac failure congestive | 1/51 (2%) | 0/19 (0%) | ||
| Cardiomyopathy NOS | 1/51 (2%) | 0/19 (0%) | ||
| Pulmonary oedema NOS | 1/51 (2%) | 1/19 (5.3%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain upper | 0/51 (0%) | 1/19 (5.3%) | ||
| Gastrointestinal haemorrhage NOS | 1/51 (2%) | 0/19 (0%) | ||
| General disorders | ||||
| Catheter site haemorrhage | 1/51 (2%) | 0/19 (0%) | ||
| Fatigue | 1/51 (2%) | 0/19 (0%) | ||
| Injection site cellulitis | 1/51 (2%) | 0/19 (0%) | ||
| Multi-organ failure | 2/51 (3.9%) | 0/19 (0%) | ||
| Pyrexia | 7/51 (13.7%) | 3/19 (15.8%) | ||
| Sudden death | 1/51 (2%) | 1/19 (5.3%) | ||
| Hepatobiliary disorders | ||||
| Cholestasis | 1/51 (2%) | 0/19 (0%) | ||
| Immune system disorders | ||||
| Hypersensitivity NOS | 0/51 (0%) | 1/19 (5.3%) | ||
| Infections and infestations | ||||
| Bronchitis acute NOS | 0/51 (0%) | 1/19 (5.3%) | ||
| Herpes zoster | 1/51 (2%) | 0/19 (0%) | ||
| Pneumonia NOS | 7/51 (13.7%) | 2/19 (10.5%) | ||
| Respiratory tract infection NOS | 7/51 (13.7%) | 2/19 (10.5%) | ||
| Septic shock | 1/51 (2%) | 0/19 (0%) | ||
| Upper respiratory tract infection NOS | 1/51 (2%) | 0/19 (0%) | ||
| Urinary tract infection NOS | 1/51 (2%) | 0/19 (0%) | ||
| Investigations | ||||
| Blood creatine phosphokinase increased | 0/51 (0%) | 2/19 (10.5%) | ||
| Metabolism and nutrition disorders | ||||
| Hypercalcaemia | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Bone pain | 1/51 (2%) | 0/19 (0%) | ||
| Muscle weakness NOS | 0/51 (0%) | 1/19 (5.3%) | ||
| Myalgia | 0/51 (0%) | 1/19 (5.3%) | ||
| Myopathy | 1/51 (2%) | 0/19 (0%) | ||
| Myopathy toxic | 0/51 (0%) | 1/19 (5.3%) | ||
| Nervous system disorders | ||||
| Cerebrovascular accident | 1/51 (2%) | 0/19 (0%) | ||
| Cervical cord compression | 1/51 (2%) | 0/19 (0%) | ||
| Cognitive disorder | 1/51 (2%) | 0/19 (0%) | ||
| Metabolic encephalopathy NOS | 1/51 (2%) | 0/19 (0%) | ||
| Parkinsonism | 1/51 (2%) | 0/19 (0%) | ||
| Quadriparesis | 1/51 (2%) | 0/19 (0%) | ||
| Psychiatric disorders | ||||
| Confusional state | 1/51 (2%) | 0/19 (0%) | ||
| Renal and urinary disorders | ||||
| Acute pre-renal failure | 1/51 (2%) | 0/19 (0%) | ||
| Renal failure NOS | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute pulmonary oedema | 1/51 (2%) | 0/19 (0%) | ||
| Bronchospasm NOS | 0/51 (0%) | 1/19 (5.3%) | ||
| Dyspnoea NOS | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Pleural effusion | 1/51 (2%) | 0/19 (0%) | ||
| Pneumonitis NOS | 1/51 (2%) | 0/19 (0%) | ||
| Pulmonary embolism | 0/51 (0%) | 1/19 (5.3%) | ||
| Respiratory failure | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Vascular disorders | ||||
| Poor peripheral circulation | 1/51 (2%) | 0/19 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Plitidepsin | Plitidepsin + Dexamethasone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 51/51 (100%) | 19/19 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia NOS | 8/51 (15.7%) | 1/19 (5.3%) | ||
| Thrombocytopenia | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 3/51 (5.9%) | 0/19 (0%) | ||
| Cardiomegaly NOS | 1/51 (2%) | 1/19 (5.3%) | ||
| Palpitations | 0/51 (0%) | 1/19 (5.3%) | ||
| Ear and labyrinth disorders | ||||
| Hypoacusis | 1/51 (2%) | 1/19 (5.3%) | ||
| Vertigo | 0/51 (0%) | 1/19 (5.3%) | ||
| Eye disorders | ||||
| Lacrimation increased | 0/51 (0%) | 1/19 (5.3%) | ||
| Vision blurred | 0/51 (0%) | 1/19 (5.3%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 1/51 (2%) | 2/19 (10.5%) | ||
| Abdominal pain NOS | 1/51 (2%) | 2/19 (10.5%) | ||
| Constipation | 8/51 (15.7%) | 1/19 (5.3%) | ||
| Diarrhoea NOS | 15/51 (29.4%) | 5/19 (26.3%) | ||
| Dyspepsia | 6/51 (11.8%) | 2/19 (10.5%) | ||
| Haemorrhoids | 0/51 (0%) | 1/19 (5.3%) | ||
| Hiatus hernia | 0/51 (0%) | 1/19 (5.3%) | ||
| Hiccups | 0/51 (0%) | 1/19 (5.3%) | ||
| Nausea | 23/51 (45.1%) | 4/19 (21.1%) | ||
| Rectal haemorrhage | 0/51 (0%) | 1/19 (5.3%) | ||
| Vomiting NOS | 13/51 (25.5%) | 2/19 (10.5%) | ||
| General disorders | ||||
| Chest pain | 0/51 (0%) | 2/19 (10.5%) | ||
| Fatigue | 38/51 (74.5%) | 16/19 (84.2%) | ||
| Injection site reaction NOS | 1/51 (2%) | 1/19 (5.3%) | ||
| Oedema peripheral | 7/51 (13.7%) | 4/19 (21.1%) | ||
| Pain NOS | 2/51 (3.9%) | 2/19 (10.5%) | ||
| Pyrexia | 20/51 (39.2%) | 3/19 (15.8%) | ||
| Rigors | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Weakness | 3/51 (5.9%) | 2/19 (10.5%) | ||
| Hepatobiliary disorders | ||||
| Hepatic disorder NOS | 0/51 (0%) | 1/19 (5.3%) | ||
| Hepatotoxicity NOS | 4/51 (7.8%) | 0/19 (0%) | ||
| Infections and infestations | ||||
| Bronchitis NOS | 1/51 (2%) | 1/19 (5.3%) | ||
| Bronchitis acute NOS | 0/51 (0%) | 1/19 (5.3%) | ||
| Herpes simplex | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Infection NOS | 4/51 (7.8%) | 0/19 (0%) | ||
| Nasopharyngitis | 3/51 (5.9%) | 0/19 (0%) | ||
| Oral candidiasis | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Respiratory tract infection NOS | 7/51 (13.7%) | 3/19 (15.8%) | ||
| Upper respiratory tract infection NOS | 4/51 (7.8%) | 3/19 (15.8%) | ||
| Urinary tract infection NOS | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Injury, poisoning and procedural complications | ||||
| Laceration | 0/51 (0%) | 1/19 (5.3%) | ||
| Investigations | ||||
| Blood amylase increased | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Blood creatine phosphokinase | 0/51 (0%) | 1/19 (5.3%) | ||
| Blood creatine phosphokinase increased | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Blood myoglobin increased | 0/51 (0%) | 1/19 (5.3%) | ||
| Glucose urine present | 0/51 (0%) | 1/19 (5.3%) | ||
| Weight decreased | 7/51 (13.7%) | 3/19 (15.8%) | ||
| X-ray NOS chest abnormal | 1/51 (2%) | 2/19 (10.5%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 17/51 (33.3%) | 6/19 (31.6%) | ||
| Fluid overload | 0/51 (0%) | 1/19 (5.3%) | ||
| Hyperglycaemia NOS | 1/51 (2%) | 1/19 (5.3%) | ||
| Hypocalcaemia | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Hypokalaemia | 4/51 (7.8%) | 0/19 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 3/51 (5.9%) | 3/19 (15.8%) | ||
| Back pain | 8/51 (15.7%) | 3/19 (15.8%) | ||
| Bone pain | 30/51 (58.8%) | 7/19 (36.8%) | ||
| Muscle cramps | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Muscle weakness NOS | 16/51 (31.4%) | 6/19 (31.6%) | ||
| Myalgia | 11/51 (21.6%) | 2/19 (10.5%) | ||
| Myopathy toxic | 0/51 (0%) | 2/19 (10.5%) | ||
| Osteonecrosis | 0/51 (0%) | 1/19 (5.3%) | ||
| Pain in limb | 3/51 (5.9%) | 2/19 (10.5%) | ||
| Nervous system disorders | ||||
| Cognitive disorder | 0/51 (0%) | 1/19 (5.3%) | ||
| Dysgeusia | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Headache NOS | 6/51 (11.8%) | 0/19 (0%) | ||
| Hypoaesthesia | 3/51 (5.9%) | 0/19 (0%) | ||
| Paraesthesia | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Peripheral neuropathy NOS | 10/51 (19.6%) | 3/19 (15.8%) | ||
| Psychiatric disorders | ||||
| Agitation | 3/51 (5.9%) | 0/19 (0%) | ||
| Anxiety | 1/51 (2%) | 1/19 (5.3%) | ||
| Confusional state | 4/51 (7.8%) | 1/19 (5.3%) | ||
| Depression | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Insomnia | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Renal and urinary disorders | ||||
| Albuminuria | 0/51 (0%) | 1/19 (5.3%) | ||
| Haematuria | 2/51 (3.9%) | 2/19 (10.5%) | ||
| Haemoglobinuria | 2/51 (3.9%) | 1/19 (5.3%) | ||
| Proteinuria | 3/51 (5.9%) | 3/19 (15.8%) | ||
| Renal failure NOS | 1/51 (2%) | 2/19 (10.5%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Catarrh | 1/51 (2%) | 1/19 (5.3%) | ||
| Cough | 9/51 (17.6%) | 3/19 (15.8%) | ||
| Dyspnoea NOS | 9/51 (17.6%) | 9/19 (47.4%) | ||
| Epistaxis | 3/51 (5.9%) | 1/19 (5.3%) | ||
| Hoarseness | 1/51 (2%) | 1/19 (5.3%) | ||
| Nasal congestion | 0/51 (0%) | 1/19 (5.3%) | ||
| Pharyngitis | 1/51 (2%) | 2/19 (10.5%) | ||
| Pleural effusion | 0/51 (0%) | 1/19 (5.3%) | ||
| Pulmonary vascular disorder NOS | 1/51 (2%) | 1/19 (5.3%) | ||
| Rhinorrhoea | 1/51 (2%) | 1/19 (5.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Folliculitis | 0/51 (0%) | 1/19 (5.3%) | ||
| Vascular disorders | ||||
| Deep venous thrombosis NOS | 0/51 (0%) | 1/19 (5.3%) | ||
| Hypotension NOS | 1/51 (2%) | 1/19 (5.3%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Claudia Silvia Corrado M.D. |
|---|---|
| Organization | PharmaMar USA Inc |
| Phone | 1 212 201 6770 |
| cscorrado@pharmamar.com |
- APL-B-014-03