A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Idasanutlin Monotherapy in Patients with Hydroxyurea-Resistant/ Intolerant Polycythemia Vera.
- Conditions
- Polycythemia Vera (PV)MedDRA version: 21.1Level: LLTClassification code 10036061Term: Polycythemia veraSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2017-000861-58-GB
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 48
- Adults > 18 years of age.
- PV according to the 2016 WHO criteria for the diagnosis of polycythemia vera.
- Hematocrit at screening and initiation of idasanutlin > 40%.
- Phlebotomy-dependent patients with splenomegaly by magnetic resonance imaging (MRI) or computerized tomography (CT) imaging (>= 450 cm3) or without splenomegaly (< 450 cm3, or prior splenectomy).
- Resistance to/intolerance to hydroxyurea according to modified ELN criteria.
- For patients in the ruxolitinib intolerant or resistant group, documentation of adverse events likely caused by ruxolitinib inadequate disease control on ruxolitinib in addition to previous hydroxyurea intolerance/resistance.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Patients must be willing to submit the blood sampling and bone marrow sampling for the PK and pharmacodynamic analyses and exploratory biomarkers.
- Adequate hepatic and renal function.
- For women of childbearing potential: agreement to or use non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 6 weeks after the last dose of idasanutlin.
- For men: Agreement to use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 90 days after the last dose of idasanutlin.
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 38
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
- Meets the criteria for post PV MF as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT).
- Blast phase disease (>20% blasts in the marrow or peripheral blood).
- Clinically-significant thrombosis within 3 months of screening.
- Patients who must receive CYP2C8 inhibitors, substrates and inducers, strong CYP3A4 inducers, or OATP1B1/3 substrates while on study. These must be discontinued 7 days (inhibitors and substrates) or 14 days (inducers) prior to start of study medication.
- Patients previously treated with MDM2 antagonist therapies
- Patients receiving interferon-alpha, anagrelide, or ruxolitinib within 28 days or 5 half-lives (whichever is shorter), or HU within 1 day, or patients receiving any other cytoreductive or investigational agents within 28 days or 5 half-lives of initial dose (whichever is shorter). Aspirin is permitted per treatment guidelines for PV unless medically contraindicated.
- Patients with evidence of electrolyte imbalance such as hypokalemia, hyperkalemia, hypocalcemia, hypercalcemia, hypomagnesemia, and hypermagnesemia of Grade > 1 intensity, as per NCI CTCAE, version 4.0 prior to dosing on Cycle 1 Day 1. Treatment for correction of electrolyte imbalances is permitted to meet eligibility.
- Neutrophil count < 1.5 × 10^9/L prior to dosing on Cycle 1 Day 1.
- Platelet count <= 150 × 10^9/L prior to dosing on Cycle 1 Day 1.
- Women who are pregnant or breastfeeding.
- Ongoing serious non-healing wound, ulcer, or bone fracture.
- History of major organ transplant.
- Uncontrolled intercurrent illness including, but not limited to hepatitis, concurrent malignancy that could affect compliance with the protocol or interpretation of results, hepatitis A, B, and C, human immunodeficiency virus (HIV)-positive, ongoing or active infection, clinically significant cardiac disease (New York Heart Association Class III or IV), symptomatic congestive heart failure, unstable angina pectoris, ventricular arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Concurrent malignancy exceptions include: Curatively treated carcinoma in situ of the cervix, good prognosis ductal carcinoma in situ of the breast, basal- or squamous cell skin cancer, Stage I melanoma, or low grade, early stage localized prostate cancer. Any previously treated early stage non hematological malignancy that has been in remission for at least 2 years is also permitted.
- Patients with active GI conditions (Crohn’s disease, ulcerative colitis, diverticulosis associated colitis, and Behçet's disease).
- Clinically significant toxicity (other than alopecia) from prior therapy that has not resolved to Grade <= 1 (according to the NCI CTCAE, v4.0) prior to Day 1 Cycle 1.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method