NAVITOCLAX for Myelofibrosis|Myeloproliferative neoplasm

Inclusion criteria

• {"criterion_text":"- Part 1 and Part 2 of the study are not being conducted within the EEA.\n- 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\n- Part 3: Subject must have an ECOG performance status ≤ 2.\n- 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.\n- 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.\n- 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.\n- Part 6: Subject must currently be receiving navitoclax in France or Bulgaria in a navitoclax clinical trial (M16-191, M19-753, or M20-178) and, in the opinion of the treating investigator, deriving clinical benefit from ongoing navitoclax treatment.\n- Part 6: Subject must have completed assessments through the End of Treatment Visit / Treatment Completion Visit in their parent protocol prior to starting navitoclax under Extension Part 6.\n- Part 4: Subject must have an ECOG performance status ≤ 2.\n- 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.\n- Part 5: Subjects with a documented diagnosis of primary MF as defined by the WHO classification, post-PV MF, or post-ET MF.\n- 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\n- Part 5: Subject must have an ECOG performance status ≤ 2.\n- Subjects ≥ 18 years old\n- Part 3: At screening or baseline (pre-dose on Day 1), subject has QTc interval by Fridericia's correction (QTcF) ≤ 450 msec.\n- 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."}

Exclusion criteria

• {"criterion_text":"- Part 1 and Part 2 of the study are not being conducted within the EEA.\n- Part 5: Subject must not have received CYP2C9 inducers within 10 days prior to the first dose of study drugs.\n- Part 3: Subject must not show leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy).\n- 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.\n- Part 3: Subject must not have had prior therapy with a BH3 mimetic compound.\n- 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.\n- Part 3: Subject must not have received strong CYP3A inducers within 10 days prior to the first dose of navitoclax.\n- Part 4: Subject must not show leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy).\"\n- 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.\n- Part 4: Subject must not have had prior therapy with a BH3 mimetic compound.\n- 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.\n- 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.\n- Part 4: Subject must not have received strong CYP3A or CYP2C9 inducers within 10 days prior to the first dose of study drugs.\n- 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.\n- 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.\n- 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.\n- 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.\n- Part 5: Subject must not have received strong CYP3A inducers within 10 days prior to the first dose of study drugs."}

Primary endpoints

• {"endpoint_text":"- Part 3: To evaluate the effect of navitoclax on corrected QTc interval by Fridericia's correction formula (QTcF) in subjects with MPN or CMML in the US and Europe.","definition_or_measurement_approach":"Measurement: corrected QTc interval by Fridericia's correction formula (QTcF) in ECG variables collected in Part 3."}
• {"endpoint_text":"- Part 4: To evaluate the effect of navitoclax, a potential CYP2C9 inhibitor, on the pharmacokinetics, safety, and tolerability of a single dose of celecoxib, a sensitive CYP2C9 substrate, in subjects with MPN or CMML.","definition_or_measurement_approach":"Measurement: pharmacokinetic assessment of celecoxib following single dose, and safety/tolerability assessments (AEs, labs, vital signs) in Part 4."}
• {"endpoint_text":"- Part 5: To evaluate the effect of navitoclax on the PK, safety, and tolerability of ruxolitinib in subjects with MF in the US and Europe.","definition_or_measurement_approach":"Measurement: pharmacokinetic assessment of ruxolitinib and safety/tolerability assessments (AEs, labs, vital signs) in Part 5."}

Secondary endpoints

• {"endpoint_text":"- Safety Endpoint: Safety evaluations include adverse event (AE) monitoring, physical examinations, vital sign measurements, electrocardiogram (ECG) variables, and clinical laboratory testing (hematology, chemistry, coagulation, and urinalysis) as a measure of safety and tolerability","definition_or_measurement_approach":"Monitoring of AEs, physical exams, vital signs, ECG variables and clinical labs (hematology, chemistry, coagulation, urinalysis)."}
• {"endpoint_text":"- Pharmacodynamic Endpoint: Part 3 only- ECG variables will include QTcF, heart rate, PR interval (time from the onset of the P wave to the start of the QRS complex), QRS duration, and waveform composition.","definition_or_measurement_approach":"ECG-derived measures: QTcF, heart rate, PR interval, QRS duration, waveform composition collected per protocol in Part 3."}
• {"endpoint_text":"- Pharmacokinetic Endpoint: Pharmacokinetic (PK) samples will be collected at specified time points and analyzed for navitoclax","definition_or_measurement_approach":"PK sampling at specified time points with analysis of navitoclax plasma concentrations (and ruxolitinib in Parts 2 and 5, celecoxib in Part 4 as applicable) to compute PK parameters."}
• {"endpoint_text":"- Efficacy Endpoint: Preliminary efficacy will be evaluated.","definition_or_measurement_approach":"Preliminary efficacy assessments as defined in protocol (not further specified in the provided record)."}

Bulgaria

Latest Decision Or Authorization Date

27-11-2024

Number Of Sites

2

Number Of Participants

24

Croatia

Latest Decision Or Authorization Date

11-11-2024

Number Of Sites

1

Number Of Participants

5

France

Latest Decision Or Authorization Date

19-02-2026

Number Of Sites

7

Number Of Participants

11

Germany

Latest Decision Or Authorization Date

06-11-2024

Number Of Sites

2

Number Of Participants

1

Italy

Latest Decision Or Authorization Date

06-11-2024

Number Of Sites

2

Number Of Participants

10

Spain

Latest Decision Or Authorization Date

11-11-2024

Number Of Sites

3

Number Of Participants

9

Primary sponsor

Full Name

AbbVie Deutschland GmbH & Co. KG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Syneos Health Clinique Inc.

Responsibilities

code 4

Name

Labcorp Central Laboratory Services S.a.r.l.

Responsibilities

kit production/supply, sample storage; code 4

Third parties

• {"country":"Canada","full_name":"Syneos Health Clinique Inc.","duties_or_roles":"code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"kit production/supply, sample storage; code 4","organisation_type":"Pharmaceutical company"}