KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment
KRT-232 Versus Best Available Therapy for the Treatment of Subjects With Myelofibrosis Who Are Relapsed or Refractory to JAK Inhibitor Treatment
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the
treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with a JAK
inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF.
This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose
and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in
the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT
(Arm 2). The BAT administered will be determined by the treating physician, with the option
to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any
time.
treatment of patients with myelofibrosis (MF) who no longer benefit from treatment with a JAK
inhibitor. Inhibition of MDM2 is a novel mechanism of action in MF.
This study will be conducted in 2 phases. Phase 2 will determine the KRT-232 recommended dose
and dosing schedule; Phase 3 will test KRT-232 vs Best Available Therapy (BAT). Patients in
the Phase 3 part of the study will be randomized 2:1 to receive either KRT-232 (Arm 1) or BAT
(Arm 2). The BAT administered will be determined by the treating physician, with the option
to "cross-over" to KRT-232 treatment after 6 months of BAT or if the disease worsens at any
time.
Hematologic,
Leukemia
Phase II
Adults
Mol. targeted/Immunotherapy/Biologics
KRT-232
Savona, Michael
National
Vanderbilt University
08-12-2019
Treatment
VICCHEM18136
NCT03662126
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
Failure of prior treatment with JAK inhibitor
ECOG 2
Exclusion Criteria:
Prior splenectomy
Splenic irradiation within 3 months prior to randomization
History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization
History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization
Prior MDM2 inhibitor therapy or p53-directed therapy
Prior allogeneic stem-cell transplant or plans for allogeneic stem cell transplant
History of major organ transplant
Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)
Confirmed diagnosis of PMF, post-PV MF or post-ET MF (WHO)
High, intermediate-2, or intermediate-1 risk Dynamic International Prognostic System (DIPSS)
Failure of prior treatment with JAK inhibitor
ECOG 2
Exclusion Criteria:
Prior splenectomy
Splenic irradiation within 3 months prior to randomization
History of major hemorrhage or intracranial hemorrhage within 6 months prior to randomization
History of stroke, reversible ischemic neurological defect or transient ischemic attack within 6 months prior to randomization
Prior MDM2 inhibitor therapy or p53-directed therapy
Prior allogeneic stem-cell transplant or plans for allogeneic stem cell transplant
History of major organ transplant
Grade 2 or higher QTc prolongation (> 480 milliseconds per NCI-CTCAE criteria, version 5.0)
