A Study Evaluating Safety and Tolerability, and Pharmacokinetics of Navitoclax Alone and in Combination With Ruxolitinib in Participants With Myeloproliferative Neoplasm

Phase 1

• Conditions: Myelofibrosis, Myeloproliferative Neoplasms; MedDRA version: 20.0Level: PTClassification code: 10028537Term: Myelofibrosis Class: 100000004864; MedDRA version: 20.0Level: PTClassification code: 10077465Term: Myeloproliferative neoplasm Class: 100000004864; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-507274-40-00
• Lead Sponsor: AbbVie Deutschland GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-07
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 85

Inclusion Criteria

Part 1 and Part 2 of the study are not being conducted within the EEA., Part 4: Subject must have an ECOG performance status = 2., Part 4: Subject must meet laboratory parameters for bone marrow reserves, platelet count, neutrophil count, renal function, hepatic function and enzymes, AST and ALT, Billirubin, coagulation and serum potassium., Part 5: Subjects with a documented diagnosis of primary MF as defined by the WHO classification, post-PV MF, or post-ET MF., Part 5: Subject must be requiring treatment for MF and must either have no prior treatment with a JAK2 inhibitor or have received treatment with ruxolitinib meeting at least one of the following criteria listed in protocol eligibility criteria, Part 5: Subject must have an ECOG performance status = 2., Subjects = 18 years old, Part 3: At screening or baseline (pre-dose on Day 1), subject has QTc interval by Fridericia's correction (QTcF) = 450 msec., Part 3: Subjects with a documented diagnosis of primary or secondary MF, ET, PV or chronic myelomonocytic leukemia (CMML) as defined by the WHO classification., Part 3: Subject must be requiring treatment and have failed or are intolerant to at least one prior therapy and be ineligible for allogeneic stem cell transplantation. Subjects who refuse standard therapy may only be enrolled in regions where permitted by local regulations, Part 3: Subject must have an ECOG performance status = 2., Part 3: Subject must meet laboratory parameters for bone marrow reserves, platelet count, neutrophil count, renal function, hepatic function and enzymes, AST and ALT, Billirubin, coagulation, serum potassium and hypocalcemia., Part 4: Subjects with a documented diagnosis of primary or secondary MF, ET, PV or chronic myelomonocytic leukemia (CMML) as defined by the WHO classification., Part 4: Subject must be requiring treatment and have failed or are intolerant to at least one prior therapy and be ineligible for allogeneic stem cell transplantation. Subjects who refuse standard therapy may only be enrolled in regions where permitted by local regulations.

Exclusion Criteria

Part 1 and Part 2 of the study are not being conducted within the EEA., Part 5: Subject must not have received CYP2C9 inducers within 10 days prior to the first dose of study drugs., Part 3: Subject must not show leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy)., Part 3: Subject must not be currently on medications that interfere with coagulation (including warfarin) or platelet function except for low-dose aspirin (up to 100 mg) and LMWH., Part 3: Subject must not have had prior therapy with a BH3 mimetic compound., Part 3: Subject must not have received strong or moderate CYP3A inhibitors within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of navitoclax., Part 3: Subject must not have received strong CYP3A inducers within 10 days prior to the first dose of navitoclax., Part 4: Subject must not show leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy)., Part 4: Subject must not be currently on medications that interfere with coagulation (including warfarin) or platelet function except for low-dose aspirin (up to 100 mg) and LMWH., Part 4: Subject must not have had prior therapy with a BH3 mimetic compound., Part 4:Subject must not have received strong or moderate CYP3A inhibitors or CYP2C9 within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of study drugs., Part 4: Subject must not have received strong or moderate CYP2C9 inhibitors within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of study drugs., Part 4: Subject must not have received strong CYP3A or CYP2C9 inducers within 10 days prior to the first dose of study drugs., Part 5: Subject must not have a history of an active malignancy other than MF within the past 2 years prior to study entry, except for: - Adequately treated in situ carcinoma of the cervix uteri - Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin - Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy., Part 5: Subject must not be currently on medications that interfere with coagulation (including warfarin) or platelet function except for low-dose aspirin (up to 100 mg) and LMWH., Part 5: Subject must not have received strong CYP3A inhibitors within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of study drugs., Part 5: Subject must not have received CYP2C9 inhibitors within 28 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of study drugs., Part 5: Subject must not have received strong CYP3A inducers within 10 days prior to the first dose of study drugs.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified