Clinical Trial of Aplidin® in Patients With Primary Myelofibrosis

Phase 2

Completed

• Conditions: Myelofibrosis
• Interventions: Drug: APLIDIN (plitidepsin)

• Registration Number: NCT01149681
• Lead Sponsor: PharmaMar

Brief Summary

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

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 Timeline

• Study First Submitted: 2010-06-22
• Study First Submitted QC: 2010-06-22
• Study First Posted: 2010-06-23
• Study Start: 2010-07
• Primary Completion: 2011-02
• Study Completion: 2011-02
• Results First Submitted: 2018-10-11
• Status Verified: 2020-09
• Results First Submitted QC: 2020-09-17
• Last Update Submitted: 2020-09-17
• Results First Posted: 2020-10-12
• Last Update Posted: 2020-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm one	APLIDIN (plitidepsin)	-

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	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	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).

Secondary Outcome Measures

Name	Time	Method
Quality of Life (QoL)	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	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.

Trial Locations

Locations (2)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Azienda Ospedaliero Universitaria Careggi di Firenze; 🇮🇹 Firenze, Italy