Selinexor has shown single-agent activity in a current phase I study enrolling patients with relapsed/refractory AML with durable complete remissions (CR), complete remissions with incomplete hematologic recovery (CRi), partial remissions (PR), and stable disease (SD) observed. Furthermore, common toxicities included nausea, fatigue, and anorexia and were manageable with supportive care agents. Additionally, CLAG chemotherapy has proven activity in relapsed and refractory AML, and has been shown to be a relatively well tolerated regimen without significant non-hematologic toxicity. Given the established role of CLAG chemotherapy, the single agent activity of selinexor, and their non-overlapping toxicities, the investigators propose a phase I/II open label study of selinexor in combination with CLAG for the treatment of patients with relapsed/refractory AML.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Washington University School of Medicine
St Louis, Missouri, United States
Safety and Tolerability of Treatment as Measured by Incidence of Grade 3-4 Adverse Events Occurring in >5% of Participants
-All adverse events will be classified using the descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Time frame: From start of treatment until 30 days following last day of study treatment or until the start of a subsequent treatment for AML, whichever came first (41 days)
Complete Remission Rate (CR + CRi)
* Morphologic complete remission (CR): neutrophil count \> 1.0 x 109 /L, platelet count ≥ 100 x 109/L, \< 5% bone marrow blasts by morphologic review, no Auer rods, no evidence of extramedullary disease. (No requirements for marrow cellularity, hemoglobin concentration). * Morphologic complete remission with incomplete blood count recovery (CRi): same as CR but ANC may be \<1000/mcl or platelet count \<100,000/mcl * Participants in the phase I portion of the study, treated at the MTD will count towards the phase II accrual goal for evaluation of the primary endpoint.
Time frame: Median follow-up of 34 days
Time to Platelet Engraftment
-Time to platelet engraftment: Defined as the date of the first dose of study drug to the date that the platelet count is \>100,000/mm\^3 in the absence of platelet transfusions.
Time frame: 56 days
Time to Neutrophil Engraftment
-Time to neutrophil engraftment: Defined as the date of the first dose of study drug to the date that the absolute neutrophil count is \>1,000/mm3
Time frame: Up to 2 years
Event-free Survival
Event-free survival (EFS): Defined as the interval from the date of first dose of study drug to date of treatment failure including progressive disease, recurrence, or discontinuation for any reason (including toxicity, patient preference, initiation of new treatment without documented progression, or death due to any cause).
Time frame: Up to 2 years (median follow-up of 307 days)
Duration of Remission
-Duration of remission (DOR): Defined as the interval from the date complete remission is documented to the date of recurrence.
Time frame: Up to 2 years
Relapse-free Survival
Relapse-free survival (RFS): For patients achieving a complete remission, defined as the interval from the date of first documentation of a leukemia free state to date of recurrence or death due to any cause.
Time frame: Median follow-up of 307 days
Overall Survival
Overall survival (OS): Defined as the date of first dose of study drug to the date of death from any cause. OS will be evaluated at 3 month intervals for at least 12 months and up to a maximum of 2 years.
Time frame: Up to 2 years (median follow-up of 307 days)
Number of Participants Who Were Able to Undergo Hematopoietic Stem Cell Transplantation
Allogeneic stem cell transplant utilization: the number of patients proceeding to allogeneic transplant within 2 months following end of study without any additional salvage therapy following study treatment.
Time frame: Up to 2 years (median follow-up of 307 days)
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