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A Open-Label Study Evaluating Tolerability and Efficacy of Navitoclax alone or in Combination with Ruxolitinib in Subjects with Myelofibrosis

Phase 1
Conditions
Myelofibrosis
MedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2017-001398-17-ES
Lead Sponsor
AbbVie Deutschland GmbH & Co. KG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
164
Inclusion Criteria

- Subjects = 18 years of age
- Subjects with documented diagnosis of Intermediate or High-risk Primary myelofibrosis, post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis
- Subject must be ineligible or unwilling to undergo stem cell transplantation at time of study entry
- Subject must have either received prior treatment with ruxolitinib OR another JAK-2 inhibitor therapy OR must not have received any prior treatment with JAK-2 inhibitor.
- Subject has palpable splenomegaly.
- Subject must meet the laboratory parameters (adequate bone marrow, renal and hepatic function) as defined in the protocol.
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion Criteria

- Splenic irradiation within 6 months prior to screening, or prior splenectomy.
- Leukemic transformation (> 10% blasts in peripheral blood or bone marrow biopsy).
- Subject is currently on medications that interfere with coagulation (including warfarin) or platelet function with the exception of low dose aspirin (up to 100 mg) and Low-molecular-weight heparin.
- Prior therapy with a BH3 mimetic compound.
- Subject has received strong or moderate CYP3A inhibitors within 14 days prior to the administration of the first dose of navitoclax.

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: Evaluate the effect of navitoclax alone or in combination with ruxolitinib on spleen volume;Secondary Objective: - To assess the effect of navitoclax alone or in combination with ruxolitinib on total symptom score (TSS) as assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0 diary<br>- To evaluate the effect of navitoclax alone or in combination with ruxolitinib on bone marrow fibrosis<br>- To determine the overall response rate (ORR = sum of rates of complete remission [CR] + partial remission [PR]) associated with navitoclax alone or in combination with ruxolitinib<br>- To determine the rate of anemia response associated with navitoclax alone or in combination with ruxolitinib<br>- To describe the safety profile and PK profile observed with navitoclax alone or in combination with ruxolitinib;Primary end point(s): The percent of subjects who achieve = 35% spleen volume reduction (SVR35) at Week 24 measured by MRI.;Timepoint(s) of evaluation of this end point: Week 24
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): The secondary endpoints are percent change in TSS; ORR; anemia response; and change in grade of bone marrow fibrosis.;Timepoint(s) of evaluation of this end point: Week 24
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