Trial Outcomes & Findings for Clinical Trial of Aplidin® in Patients With Primary Myelofibrosis (NCT NCT01149681)
NCT ID: NCT01149681
Last Updated: 2020-10-12
Results Overview
Objective response rate (ORR) of plitidepsin in patients with: primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. ORR according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response criteria (Tefferi et al., 2006) in the evaluable population: defined as a confirmed disease response, on two consecutive evaluations performed at least eight weeks apart. Overall response (OR) = Complete Response (CR) + Partial response (PR) + Clinical improvement (CI).
COMPLETED
PHASE2
12 participants
All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured first
2020-10-12
Participant Flow
Participant milestones
| Measure |
Aplidin®
APLIDIN (plitidepsin): Aplidin® (plitidepsin) lyophilized powder and solvent for concentrate for solution for infusion. (2 mg plitidepsin vial and 4 ml ampoule).
Plitidepsin will be administered at 5 mg/m2 intravenously diluted to a total volume of 250 ml in 0.9% saline or 5% dextrose solution on Day 1 and 15 every four weeks for a maximum period of 6 cycles.
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
12
|
Reasons for withdrawal
| Measure |
Aplidin®
APLIDIN (plitidepsin): Aplidin® (plitidepsin) lyophilized powder and solvent for concentrate for solution for infusion. (2 mg plitidepsin vial and 4 ml ampoule).
Plitidepsin will be administered at 5 mg/m2 intravenously diluted to a total volume of 250 ml in 0.9% saline or 5% dextrose solution on Day 1 and 15 every four weeks for a maximum period of 6 cycles.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
7
|
|
Overall Study
Progressive disease
|
1
|
|
Overall Study
Physician Decision
|
2
|
|
Overall Study
adverse events nonrelated study drug
|
2
|
Baseline Characteristics
Clinical Trial of Aplidin® in Patients With Primary Myelofibrosis
Baseline characteristics by cohort
| Measure |
Aplidin®
n=12 Participants
APLIDIN (plitidepsin): Aplidin® (plitidepsin) lyophilized powder and solvent for concentrate for solution for infusion. (2 mg plitidepsin vial and 4 ml ampoule).
Plitidepsin will be administered at 5 mg/m2 intravenously diluted to a total volume of 250 ml in 0.9% saline or 5% dextrose solution on Day 1 and 15 every four weeks for a maximum period of 6 cycles.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
10 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured firstPopulation: 1 of the 12 patients treated was excluded. This patient received 1 complete infusion of plitidepsin in Cycle 1, and had the second infusion interrupted due to plitidepsin-related grade 3 chest and epigastric pain (reported as SAEs). Although the episode resolved a day later, she refused to continue treatment and had no disease evaluations done
Objective response rate (ORR) of plitidepsin in patients with: primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. ORR according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) response criteria (Tefferi et al., 2006) in the evaluable population: defined as a confirmed disease response, on two consecutive evaluations performed at least eight weeks apart. Overall response (OR) = Complete Response (CR) + Partial response (PR) + Clinical improvement (CI).
Outcome measures
| Measure |
Arm One
n=11 Participants
APLIDIN (plitidepsin): Aplidin® (plitidepsin) lyophilized powder and solvent for concentrate for solution for infusion. (2 mg plitidepsin vial and 4 ml ampoule).
Plitidepsin will be administered at 5 mg/m2 intravenously diluted to a total volume of 250 ml in 0.9% saline or 5% dextrose solution on Day 1 and 15 every four weeks for a maximum period of 6 cycles.
|
|---|---|
|
Objective Response Rate (ORR)
Clinical improvement
|
1 Participants
|
|
Objective Response Rate (ORR)
Stable disease
|
9 Participants
|
|
Objective Response Rate (ORR)
Progressive disease
|
1 Participants
|
SECONDARY outcome
Timeframe: All patients were followed up to progressive disease, start of a new anti-cancer therapy, death or one year after the last treatment visit of the last patient, whichever occured firstQuality of life (QoL) and symptoms assessment according to the Myelofibrosis Symptom Assessment Form (MFSAF), after treatment with plitidepsin. For full details please refer to Mesa RA, Schwager S, Radia D, Cheville A, Hussein K, Niblack J, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res 2009;33(9):1199-203. Scale measures: 0 to 10 (0 if absent) ranking being 1 the most favorable and 10 least favorable.
Outcome measures
| Measure |
Arm One
n=12 Participants
APLIDIN (plitidepsin): Aplidin® (plitidepsin) lyophilized powder and solvent for concentrate for solution for infusion. (2 mg plitidepsin vial and 4 ml ampoule).
Plitidepsin will be administered at 5 mg/m2 intravenously diluted to a total volume of 250 ml in 0.9% saline or 5% dextrose solution on Day 1 and 15 every four weeks for a maximum period of 6 cycles.
|
|---|---|
|
Quality of Life (QoL)
Overall quality of life - Baseline
|
5.7 score on a scale
Interval 4.8 to 6.6
|
|
Quality of Life (QoL)
Overall quality of life - Cycle 1
|
5.0 score on a scale
Interval 4.1 to 5.9
|
|
Quality of Life (QoL)
Overall quality of life - Cycle 2
|
5.4 score on a scale
Interval 3.8 to 6.9
|
|
Quality of Life (QoL)
Overall quality of life - Cycle 3
|
6.3 score on a scale
Interval 3.5 to 9.2
|
|
Quality of Life (QoL)
Overall quality of life - Cycle 4
|
7.5 score on a scale
Interval -24.3 to 39.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: All patients were followed up to progressive disease or death, whichever occured first, up to 30 days after their last dosePopulation: 1 of the 12 patients treated was excluded. This patient received 1 complete infusion of plitidepsin in Cycle 1, and had the second infusion interrupted due to plitidepsin-related grade 3 chest and epigastric pain (reported as SAEs). Although the episode resolved a day later, she refused to continue treatment and had no disease evaluations done
Progression free survival (PFS) is defined as the time from start of treatment to the date of documented progressive disease (PD) by IWG-MRT criteria or death (regardless of the cause of death), whichever comes first. Patients who progress or die will be considered to have had an event, except if this event occurs after the start of subsequent antitumor therapy, in which case the patient will be censored at the time of last disease assessment prior to or on the first day of the first subsequent antitumor therapy. If the patient is lost for the assessment of progression during the follow-up period, or has more than one missing follow-up between the date of last tumor assessment and the date of progression, death or further antitumor therapy, the PFS will be censored at the date of last valid disease assessment before the missing evaluations.
Outcome measures
| Measure |
Arm One
n=11 Participants
APLIDIN (plitidepsin): Aplidin® (plitidepsin) lyophilized powder and solvent for concentrate for solution for infusion. (2 mg plitidepsin vial and 4 ml ampoule).
Plitidepsin will be administered at 5 mg/m2 intravenously diluted to a total volume of 250 ml in 0.9% saline or 5% dextrose solution on Day 1 and 15 every four weeks for a maximum period of 6 cycles.
|
|---|---|
|
Progression-free Survival (PFS)
|
4.6 months
Interval 1.4 to 4.6
|
Adverse Events
Aplidin®
Serious adverse events
| Measure |
Aplidin®
n=12 participants at risk
APLIDIN (plitidepsin): Aplidin® (plitidepsin) lyophilized powder and solvent for concentrate for solution for infusion. (2 mg plitidepsin vial and 4 ml ampoule).
Plitidepsin will be administered at 5 mg/m2 intravenously diluted to a total volume of 250 ml in 0.9% saline or 5% dextrose solution on Day 1 and 15 every four weeks for a maximum period of 6 cycles.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
1/12
|
|
Cardiac disorders
Acute myocardial infarction
|
8.3%
1/12
|
|
Gastrointestinal disorders
Abdominal pain upper
|
8.3%
1/12
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
16.7%
2/12
|
|
Gastrointestinal disorders
Oesophageal varices haemorrhage
|
8.3%
1/12
|
|
General disorders
Chest pain
|
8.3%
1/12
|
|
Infections and infestations
Bronchopneumonia
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
8.3%
1/12
|
|
Vascular disorders
Deep vein thrombosis
|
8.3%
1/12
|
Other adverse events
| Measure |
Aplidin®
n=12 participants at risk
APLIDIN (plitidepsin): Aplidin® (plitidepsin) lyophilized powder and solvent for concentrate for solution for infusion. (2 mg plitidepsin vial and 4 ml ampoule).
Plitidepsin will be administered at 5 mg/m2 intravenously diluted to a total volume of 250 ml in 0.9% saline or 5% dextrose solution on Day 1 and 15 every four weeks for a maximum period of 6 cycles.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
8.3%
1/12
|
|
Blood and lymphatic system disorders
Neutropenia
|
8.3%
1/12
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
8.3%
1/12
|
|
Cardiac disorders
Aortic valve disease
|
8.3%
1/12
|
|
Cardiac disorders
Mitral valve incompetence
|
8.3%
1/12
|
|
Cardiac disorders
Palpitations
|
8.3%
1/12
|
|
Cardiac disorders
Sinus arrhythmia
|
8.3%
1/12
|
|
Cardiac disorders
Sinus bradycardia
|
8.3%
1/12
|
|
Cardiac disorders
Sinus tachycardia
|
8.3%
1/12
|
|
Eye disorders
Ocular hyperaemia
|
8.3%
1/12
|
|
Gastrointestinal disorders
Abdominal pain
|
66.7%
8/12
|
|
Gastrointestinal disorders
Diarrhoea
|
41.7%
5/12
|
|
Gastrointestinal disorders
Faeces discoloured
|
8.3%
1/12
|
|
Gastrointestinal disorders
Nausea
|
83.3%
10/12
|
|
Gastrointestinal disorders
Vomiting
|
41.7%
5/12
|
|
General disorders
Early satiety
|
66.7%
8/12
|
|
General disorders
Fatigue
|
100.0%
12/12
|
|
General disorders
Infusion related reaction
|
8.3%
1/12
|
|
General disorders
Oedema
|
25.0%
3/12
|
|
General disorders
Oedema peripheral
|
8.3%
1/12
|
|
General disorders
Pyrexia
|
16.7%
2/12
|
|
Infections and infestations
Bronchitis
|
8.3%
1/12
|
|
Infections and infestations
Cellulitis
|
8.3%
1/12
|
|
Investigations
Blood creatine phosphokinase increased
|
8.3%
1/12
|
|
Investigations
Blood creatinine increased
|
8.3%
1/12
|
|
Investigations
Ejection fraction decreased
|
8.3%
1/12
|
|
Investigations
Electrocardiogram QT prolonged
|
25.0%
3/12
|
|
Investigations
Electrocardiogram T wave abnormal
|
16.7%
2/12
|
|
Investigations
Troponin T increased
|
8.3%
1/12
|
|
Investigations
Weight decreased
|
58.3%
7/12
|
|
Metabolism and nutrition disorders
Anorexia
|
8.3%
1/12
|
|
Metabolism and nutrition disorders
Gout
|
8.3%
1/12
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
8.3%
1/12
|
|
Metabolism and nutrition disorders
Iron overload
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
16.7%
2/12
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
50.0%
6/12
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
8.3%
1/12
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
41.7%
5/12
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
8.3%
1/12
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
|
8.3%
1/12
|
|
Nervous system disorders
Balance disorder
|
8.3%
1/12
|
|
Nervous system disorders
Dizziness
|
8.3%
1/12
|
|
Nervous system disorders
Dysgeusia
|
8.3%
1/12
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
16.7%
2/12
|
|
Psychiatric disorders
Insomnia
|
16.7%
2/12
|
|
Renal and urinary disorders
Haematuria
|
8.3%
1/12
|
|
Renal and urinary disorders
Micturition urgency
|
8.3%
1/12
|
|
Renal and urinary disorders
Pollakiuria
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.3%
1/12
|
|
Respiratory, thoracic and mediastinal disorders
Emphysema
|
8.3%
1/12
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.3%
1/12
|
|
Skin and subcutaneous tissue disorders
Erythema
|
8.3%
1/12
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
58.3%
7/12
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
33.3%
4/12
|
|
Skin and subcutaneous tissue disorders
Rash macular
|
8.3%
1/12
|
|
Vascular disorders
Deep vein thrombosis
|
8.3%
1/12
|
|
Vascular disorders
Hypertension
|
16.7%
2/12
|
|
Vascular disorders
Pallor
|
8.3%
1/12
|
Additional Information
Clinical Development Department of PharmaMar´s Oncology,Business Unit.,
Pharma Mar, S.A.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60