A Phase 2 Single-Arm, Open-Label Study Evaluating Tolerability and Efficacy of Navitoclax in Combination with Ruxolitinib in Subjects with Myelofibrosis

NOT ENROLLING
Protocol # :
17-487
Conditions
Myelofibrosis (MF)
Phase
II
Disease Sites
Other Hematopoietic
Non-Hodgkin's Lymphoma
Hodgkin's Lymphoma
Lymphoid Leukemia
Myeloid and Monocytic Leukemia
Leukemia, other
Principal Investigator
Garcia, Jacqueline, S

Trial Description

This is a Phase 2 open-label, multicenter study evaluating tolerability and efficacy of
navitoclax alone or when added to ruxolitinib in participants with myelofibrosis.

Eligibility Requirements

Inclusion Criteria:

- Participants with documented diagnosis of intermediate-2 or high-risk primary
Myelofibrosis, Post Polycythemia Vera Myelofibrosis or Post-essential
Thrombocythemia Myelofibrosis.

- Participant must be ineligible due to age, comorbidities, or unfit for unrelated or
unmatched donor transplantation or unwilling to undergo stem cell transplantation at
time of study entry.

- Eastern Cooperative Oncology Group (ECOG) of 0, 1, or 2.

- Prior treatment must meet at least one of the following criteria:

- Prior or current treatment with ruxolitinib and no prior treatment with a
Bromodomain and Extra-Terminal motif (BET) proteins inhibitor or another Janus
Kinase 2 (JAK-2) inhibitor, and meet all of the following criteria:

- Ruxolitinib treatment must meet at least one of the following criteria:

- Ruxolitinib treatment for >=24 weeks with lack of efficacy defined as
a lack of spleen response (refractory) or a loss of spleen or symptom
response (relapsed)

- Ruxolitinib treatment for <24 weeks with documented disease
progression on spleen measurements while on ruxolitinib as defined in
the protocol:

- Ruxolitinib treatment for >=28 days with intolerance defined as new
red blood cell transfusion requirement (at least 2 units/month for 2
months) while receiving a total daily ruxolitinib dose of >=30 mg but
unable to reduce dose further due to lack of efficacy.

- If receiving ruxolitinib at the time of screening, must currently be on a
stable dose >=10 mg twice daily of ruxolitinib for >=4 weeks prior to the
1st dose of navitoclax.

- Participant has at least 2 symptoms each with a score >=3 or a total score
of >=12, as measured by the Myelofibrosis Symptom Assessment Form (MFSAF)
v4.0 on at least 4 out of 7 days during screening prior to study drug
dosing; OR

- Prior treatment with a JAK-2 inhibitor and meet one of the following criteria:

- Prior treatment with a JAK-2 inhibitor for at least 12 weeks

- Prior treatment with a JAK-2 inhibitor for >=28 days complicated by either
development of red blood cell transfusion requirement (at least 2
units/month for 2 months) OR Grade >= 3 adverse events of
thrombocytopenia, anemia, hematoma and/or hemorrhage while on JAK-2
inhibitor treatment; OR

- No prior treatment with a JAK-2 or BET inhibitor.

- Participant has splenomegaly as defined in the protocol.

- Participant must meet the laboratory parameters (adequate bone marrow, renal and
hepatic function) as defined in the protocol.

Exclusion Criteria:

- Splenic irradiation within 6 months prior to screening, or prior splenectomy.

- Leukemic transformation (> 10% blasts in peripheral blood or bone marrow
aspirate/biopsy).

- Participant is currently on medications that interfere with coagulation (including
warfarin) or platelet function within 3 days prior to the first dose of study drug
or during the study treatment period with the exception of low dose aspirin (up to
100 mg/day) and low-molecular-weight heparin.

- Prior therapy with a BH3 mimetic compound or stem cell transplantation.

- Participant has received strong CYP3A inhibitors (e.g., ketoconazole,
clarithromycin) or moderate CYP3A inhibitors (e.g., fluconazole) within 14 days
prior to the administration of the first dose of study drug.

17-487