Clinical Trial of Aplidin® in Patients With Primary Myelofibrosis

Study Overview
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Brief Summary
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This is an open-label, Phase II Clinical Trial of Aplidin® (plitidepsin) in Patients with Primary Myelofibrosis and post polycythemia vera/essential thrombocythemia (Post-PV/ET) Myelofibrosis.

Detailed Description
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This trial tries to assess response rate (ORR) of plitidepsin in patients with: primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF). Besides, the study results will allow to evaluate the effect of plitidepsin on bone marrow (BM) or peripheral blood histology and to determine the quality of life (QoL) and symptoms or participant patients.

Official Title
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Open-label, Phase II Clinical Trial of Aplidin® (Plitidepsin) in Patients With Primary Myelofibrosis (PMF) and Post Polycythemia Vera/Essential Thrombocythemia (Post-PV/ET) Myelofibrosis

Conditions
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Myelofibrosis

Intervention / Treatment
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* Drug: APLIDIN (plitidepsin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Primary Myelofibrosis (PMF) or Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis(post-ET/PV MF) as per revised World Health Organization (WHO) criteria. High-risk or intermediate-2 risk Myelofibrosis (MF) as defined by the International Prognostic Scoring System (IPSS); or intermediate-I risk MF associated with symptomatic splenomegaly/hepatomegaly and/or unresponsive to available therapy. At least 18 years of age, with life expectancy of ≥12 weeks. Able to provide informed consent and being willing to sign an informed consent form (ICF). Eastern Cooperative Oncology Group (ECOG) performance status ≤2. Evidence of acceptable organ function within seven days of initiating study drug Exclusion Criteria: Previous treatment with plitidepsin. Any of the following therapies within two weeks prior to initiation of study drug: chemotherapy (e.g., hydroxyurea), immunomodulatory drug therapy (e.g., thalidomide), immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or erythropoietin. Incomplete recovery from major surgery within four weeks of study entry. Radiation therapy within four weeks of study entry. Women of childbearing potential Women who are pregnant or are currently breastfeeding. Myopathy grade > 2 Known positive status for human immunodeficiency virus (HIV). Active hepatitis B or C virus (HBV or HCV) infection Diagnosis of another invasive malignancy Any acute active infection. Known hypersensitivity to the study drug or any of its formulation components (e.g., Cremophor®). Treatment with any investigational product in the 30 days before inclusion in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm one<br> | Drug: APLIDIN (plitidepsin)<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | 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). | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (QoL) | Quality 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aplidin, Plitidepsin, Myelofibrosis, Pharma Mar