A Phase 2, open label, dose regimen ranging clinical study to determine the safety and efficacy of INCB018424 in patients with advanced polycythemia vera or essential thrombocythemia refractory to hydroxyurea - ND

• Register: EUCTR
• Last refreshed on: 23 November 2020
• Main ID: EUCTR2008-001382-28-IT
• Date of registration: 01/10/2008
• Prospective Registration: No
• Primary sponsor: Incyte Corporation
• Public title: A Phase 2, open label, dose regimen ranging clinical study to determine the safety and efficacy of INCB018424 in patients with advanced polycythemia vera or essential thrombocythemia refractory to hydroxyurea - ND
• Scientific title: A Phase 2, open label, dose regimen ranging clinical study to determine the safety and efficacy of INCB018424 in patients with advanced polycythemia vera or essential thrombocythemia refractory to hydroxyurea - ND
• Date of first enrolment: 19/09/2008
• Target sample size: 105
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-001382-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Italy

Key inclusion & exclusion criteria

Inclusion criteria:
Must be at least 18 years of age 2. Confirmed diagnosis of polycythemia vera or essential thrombocythemia as determined by treating physician (Guidelines in Appendix 10 and 11) 3. Patients should have disease refractory to hydroxyurea or for whom treatment with hydroxyurea is contraindicated as determined by the treating physician. Disease must be assessed within 21 days prior to treatment initiation. or Patients who have refused further treatment with hydroxyurea due to side effects. These patients must have had a trial with hydroxyurea, and the treating physician must concur that discontinuing hydroxyurea is in the best interest of the patient. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 5. Required baseline laboratory data include: a) Hct > 45% for PV or phlebotomy required two times in prior six months with at least one occurrence in prior three months b) Platelet count ≥ 125 x 109/L for PV patients c) Platelet count > 650 x109/L for ET patients unless receiving treatment d) Absolute neutrophil count (ANC) ≥ 1.2 x 109/L for both patient groups e) Total bilirubin ≤ 2 x institutional upper limit of normal (ULN) for both patient groups f) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN for both patient groups g) Serum creatinine ≤ 2 x ULN for both patient groups 6. Females will be either postmenopausal for at least 1 year with documented follicle stimulating hormone (FSH) > 30 IU/L or surgically sterile for at least 3 months OR females of childbearing potential who agree to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from Screening through Follow-up. (Note: Permitted methods which are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed). For all females, the urine pregnancy test result must be negative at Screening. Males must agree to take appropriate precautions to avoid fathering a child (with at least 99% certainty) from Screening through Follow-up. (Note: Permitted methods which are at least 99% effective in preventing pregnancy should be communicated to the subjects and their understanding confirmed.) 7. Is able to comprehend and is willing to sign an informed consent form, indicating that the patient is aware of the nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomfort. 8. Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
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:
Females who are pregnant or are currently breastfeeding 2. Treatment with interferon alpha or anagrelide within 7 days and hydroxyurea within 1 day of starting INCB018424. All other cytoreductive therapies for PV or ET or investigational medications must be discontinued within 28 days of enrollment. 3. Patients diagnosed with another malignancy unless the malignancy was cervical intraepithelial neoplasia or basal or squamous cell skin cancer and the patient has been disease free for > 3 years, unless approved by Sponsor. 4. Patients receiving therapy with intermediate or high dose steroids greater than the equivalent of 10 mg prednisone per day 5. Patients with known active hepatitis A, B, C or known positivity for HIV 6. Uncontrolled inter-current illness or has any concurrent condition that, in the Investigator?s opinion, would jeopardize the safety of the patient or compliance with the protocol. 7. Clinically significant cardiac disease (NYHA Class III or IV) 8. Incomplete recovery from any prior surgical procedures or had surgery within 4 weeks prior to study entry 9. Presence of acute active infection requiring systemic antimicrobials 10. Any current or planned therapy with CYP3A4 inhibitors or inducers unless approved by the Sponsor 11. Prior treatment with any oral JAK inhibitor is not permitted unless agreed to by both the investigator and the Sponsor.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

advanced polycythemia vera or essential thrombocythemia refractory to hydroxyurea
MedDRA version: 9.1 Level: LLT Classification code 10036057 Term: Polycythaemia vera
MedDRA version: 9.1 Level: LLT Classification code 10015494 Term: Essential thrombocythemia

Intervention(s)

Product Code: INCB018424
Pharmaceutical Form: Tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Code: INCB018424
Pharmaceutical Form: Tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): Primary Endpoints for PV Patients 1. Complete, partial and overall (CR + PR) response rates will be assessed for all PV patients treated with INCB018424. Response will be assessed at individual time points, but to be a confirmed response, it must be sustained for at least 2 months. Safety and tolerability as assessed by monitoring frequency, duration, and severity of adverse events graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3, and the results of laboratory, electrocardiogram findings, vital sign measurements and physical examinations. Primary Endpoints for ET Patients 1. Complete, partial and overall (CR+PR) response rates will be assessed for all ET patients treated with INCB018424. Response will be assessed at individual time points but to be a confirmed response it must be sustained for at least 2 months. Safety and tolerability as assessed by monitoring frequency, duration, and severity of adverse events graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3, and the results of laboratory, electrocardiogram findings, vital sign measurements and physical examinations.

Secondary Objective: To evaluate the relationship of changes in plasma and whole blood PD biomarkers; JAK2V617F burden in blood; and morphological, cytogenetic, and mutational status of the bone marrow to clinical outcome and to plasma concentrations of INCB018424 To evaluate the quality of life (QOL) in each patient population by specifically assessing symptoms associated with PV and ET and by using the validated EORTC QLQC30, and by evaluating the relationship of changes in those measures to treatment response

Main Objective: To evaluate the safety and efficacy profile of three different treatment regimens of INCB018424 administered to two groups of patients; those with polycythemia vera (PV) and those with essential thrombocythemia (ET). Patients in each group will be refractory to hydroxyurea or for whom hydroxyurea is contraindicated.

Secondary ID(s)

INCB 18424-256

Ethics review

Status: Approved
Approval date: 11/08/2008
Contact: