Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Nave Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
Study of Navtemadlin add-on to Ruxolitinib in JAK Inhibitor-Nave Patients With Myelofibrosis Who Have a Suboptimal Response to Ruxolitinib
This clinical trial is evaluating whether addition of navtemadlin to ruxolitinib treatment will provide more clinical benefit than ruxolitinib alone for patients with Myelofibrosis who have a suboptimal response to ruxolitinib treatment alone.
Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.
Subjects will start by receiving ruxolitinib alone in the run-in period. Those who demostrate a suboptimal response from ruxolitinib alone will then be randomized 2:1 to receive navtemadlin or navtemadlin placebo as add-on treatment to their ongoing ruxolitinib. Randomized means that subjects will be assigned to a group by chance, like a flip of a coin. The study is blinded, meaning the subjects, doctors, central endpoint assessors and sponsor will not know which add on treatment (navtemadlin or navtemadlin placebo) the subject is receiving.
Hematologic
Phase III
Adults
Mol. targeted/Immunotherapy/Biologics
Navtemadilin,
Placebo,
Ruxolitinib
Mohan, Sanjay
National
Vanderbilt University
08-25-2025
Eligibility
18 Years and older
ALL
false
Inclusion Criteria:
Inclusion Criteria for Ruxolitinib Alone Period:
Inclusion Criteria for Ruxolitinib Alone Period:
Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
JAK-inhibitor treatment naive
JAK-inhibitor treatment naive
Exclusion Criteria:
Exclusion Criteria for Ruxolitinib Alone Period:
Exclusion Criteria for Ruxolitinib Alone Period:
Prior Splenectomy
Prior Splenectomy
Splenic irradiation within 3 months prior to the first dose
Splenic irradiation within 3 months prior to the first dose
Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
Eligible for Bone Marrow Transplant
Eligible for Bone Marrow Transplant
Peripheral blood or bone marrow blast count 10 percent
Peripheral blood or bone marrow blast count 10 percent
Inclusion Criteria for Randomized Period:
Inclusion Criteria for Randomized Period:
PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
ECOG performance status of 0 to 2
ECOG performance status of 0 to 2
Treatment with a stable dose of ruxolitinib
Treatment with a stable dose of ruxolitinib
Suboptimal response to run-in ruxolitinib treatment
Suboptimal response to run-in ruxolitinib treatment
Exclusion Criteria for Randomized Period:
Exclusion Criteria for Randomized Period:
Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 10\^9/L
Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 10\^9/L
Peripheral blood or bone marrow blast count 10 percent
Peripheral blood or bone marrow blast count 10 percent
Inclusion Criteria for Ruxolitinib Alone Period:
Inclusion Criteria for Ruxolitinib Alone Period:
Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
Confirmed diagnosis of PMF, post-PV MF, or post-ET MF, as assessed by the treating physician according to the World Health Organization (WHO) criteria
High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
High, Intermediate-1, Intermediate-2 risk category International Prognosis System Score (IPSS)
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
JAK-inhibitor treatment naive
JAK-inhibitor treatment naive
Exclusion Criteria:
Exclusion Criteria for Ruxolitinib Alone Period:
Exclusion Criteria for Ruxolitinib Alone Period:
Prior Splenectomy
Prior Splenectomy
Splenic irradiation within 3 months prior to the first dose
Splenic irradiation within 3 months prior to the first dose
Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
Prior BCL-XL, BET, MDM2, PI3K, PIM, or XPO1 inhibitors therapy or p53-directed therapy
Eligible for Bone Marrow Transplant
Eligible for Bone Marrow Transplant
Peripheral blood or bone marrow blast count 10 percent
Peripheral blood or bone marrow blast count 10 percent
Inclusion Criteria for Randomized Period:
Inclusion Criteria for Randomized Period:
PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
PMF, post-PV MF, or post-ET MF that is TP53WT as assessed by central testing
ECOG performance status of 0 to 2
ECOG performance status of 0 to 2
Treatment with a stable dose of ruxolitinib
Treatment with a stable dose of ruxolitinib
Suboptimal response to run-in ruxolitinib treatment
Suboptimal response to run-in ruxolitinib treatment
Exclusion Criteria for Randomized Period:
Exclusion Criteria for Randomized Period:
Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 10\^9/L
Elevated white blood cell count that doubles (or more) during ruxolitinib treatment and exceeds 50 10\^9/L
Peripheral blood or bone marrow blast count 10 percent
Peripheral blood or bone marrow blast count 10 percent
