None listed
Conditions
Interventions
Product Name: Aplidin
Pharmaceutical Form: Powder for infusion*
INN or Proposed INN: Plitidepsin
CAS Number: 137219-37-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration num
Sponsors
PHARMA MAR
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Diagnosis of PMF or post-ET/PV MF as per revised World Health Organization (WHO) criteria (Appendix 3). 2)High-risk or intermediate-2 risk MF as defined by the International Prognostic Scoring System (IPSS) (Appendix 4); or intermediate-I risk MF associated with symptomatic splenomegaly/hepatomegaly and/or unresponsive to available therapy. 3)At least 18 years of age, with life expectancy of >/=12 weeks. 4)Able to provide informed consent and being willing to sign an informed consent form (ICF). 5)Eastern Cooperative Oncology Group (ECOG) performance status /= 1.0 x 10^9/L. d)Platelet count >/= 25 x 10^9/L. e)Left ventricular ejection fraction (LVEF) within normal limits. f)Creatine phosphokinase (CPK) /= 40 mL/min. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Previous treatment with plitidepsin. 2.Any of the following therapies within two weeks prior to initiation of study drug: a)chemotherapy (e.g., hydroxyurea), b)immunomodulatory drug therapy (e.g., thalidomide), c)immunosuppressive therapy, d)corticosteroids >10 mg/day prednisone or equivalent, or e)erythropoietin. 3.Incomplete recovery from major surgery within four weeks of study entry. 4.Radiation therapy within four weeks of study entry. 5.Women of childbearing potential, unless surgically sterile for at least three months (i.e., hysterectomy), or postmenopausal for at least 12 months (follicle-stimulating hormone, FSH > 30 U/mL), or unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) throughout the treatment period and for six months after discontinuation of the treatment. Permitted methods for preventing pregnancy must be communicated to the study patients and their understanding has to be confirmed. 6. Men who partner with a woman of childbearing potential, unless they agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) throughout the treatment period and for six months after discontinuation of the treatment. Permitted methods for preventing pregnancy must be communicated to the study subjects and their understanding has to be confirmed. 7.Women who are pregnant or are currently breastfeeding. 8.Myopathy grade > 2 or any clinical situation that causes significant and persistent elevation of CPK (> 2.5 x ULN in two different determinations performed one week apart). 9.Known positive status for human immunodeficiency virus (HIV). 10.Active hepatitis B or C virus (HBV or HCV) infection and/or significant non-neoplastic liver disease (i.e. cirrhosis). 11.Diagnosis of another invasive malignancy unless free of disease for at least three years following therapy with curative intent. Patients with early-stage basal cell or squamous cell skin cancer, cervical intraepithelial neoplasia, cervical carcinoma in situ, or superficial bladder cancer, may be eligible to participate at the Investigator`s discretion. 12.Any acute active infection. 13.Serious concomitant systemic disorders that would compromise the safety of the patient or limit the patient’s ability to complete or comply with the study, including: a)Uncontrolled medical illness that the Investigator feels will compromise the patient’s tolerance to the study medication. b)Uncontrolled or unstable angina, myocardial infarction, cerebrovascular accident, valvular heart disease or congestive heart failure (New York Heart Association Classification 3 or 4), within 12 months prior to initiation of study drug. c)Pulmonary embolism within three months prior to initiation of study drug. d)Uncontrolled arterial hypertension (>/= 160/110 mmHg) despite optimal medical therapy. e)Previous treatment with doxorubicin at cumulative doses >/= 450 mg/m2. f)Symptomatic arrhythmia (excluding anemia-related sinusal tachycardia grade 450 msec for men or >470 msec for women at pre-study screening, unless attributable to pre-existing bundle branch block. 14.Known hypersensitivity to the study drug or any of its formulation components (e.g., Cremophor). 15.Treatment with any investigational product in the 30 days before inclusion in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the objective response rate (ORR) of plitidepsin according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT, Appendix 1) in patients with: - primary myelofibrosis (PMF), - post-polycythemia vera myelofibrosis (post-PV MF), or - post-essential thrombocythemia myelofibrosis (post-ET MF).;Secondary Objective: 1- To evaluate the safety and tolerability of plitidepsin in this study population. 2- To determine the effect of plitidepsin on: - bone marrow (BM) or peripheral blood histologic and cytogenetic findings, and - peripheral blood granulocyte JAK2V617F allele burden. 3- To determine the quality of life (QoL) and symptoms assessment according to the Myelofibrosis Symptom Assessment Form (MFSAF) (Appendix 2), after treatment with plitidepsin.;Primary end point(s): The primary endpoint of this trial is the treatment success rate, with success defined as confirmed disease response. A confirmed response is deemed to be an objective status of complete response (CR), partial response (PR), or clinical improvement (CI), according to the IWG-MRT consensus criteria (i.e., on two consecutive evaluations performed at least eight weeks apart). | — |
Countries
Italy
Outcome results
None listed