Clinical Trial of Aplidin® in Patients With Primary Myelofibrosis

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

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.

Study Overview

• Status: Completed
• Conditions: Myelofibrosis
• Intervention / Treatment: Drug: APLIDIN (plitidepsin)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Firenze, Italy, 50134
    • Azienda Ospedaliero UNIVERSITARIA CAREGGI DI FIRENZE
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of Primary Myelofibrosis (PMF) or Post Polycythemia Vera/Essential Thrombocythemia Myelofibrosis(post-ET/PV MF) as per revised World Health Organization (WHO) criteria.
2. 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.
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 ≤2.
6. Evidence of acceptable organ function within seven days of initiating study drug

Exclusion Criteria:

1. Previous treatment with plitidepsin.

2. 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.
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
6. Women who are pregnant or are currently breastfeeding.
7. Myopathy grade > 2
8. Known positive status for human immunodeficiency virus (HIV).
9. Active hepatitis B or C virus (HBV or HCV) infection
10. Diagnosis of another invasive malignancy
11. Any acute active infection.
12. Known hypersensitivity to the study drug or any of its formulation components (e.g., Cremophor®).
13. Treatment with any investigational product in the 30 days before inclusion in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm one	Drug: 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	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.	All patients were followed up to progressive disease or death, whichever occured first, up to 30 days after their last dose

Collaborators and Investigators

• Sponsor: PharmaMar

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): February 1, 2011
• Study Completion (ACTUAL): February 1, 2011

Study Registration Dates

• First Submitted: June 22, 2010
• First Submitted That Met QC Criteria: June 22, 2010
• First Posted (ESTIMATE): June 23, 2010

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2020
• Last Update Submitted That Met QC Criteria: September 17, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Myelofibrosis; Pharma Mar; Aplidin; Plitidepsin
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Primary Myelofibrosis
• Other Study ID Numbers: APL-B-020-10