This phase I trial tests the safety, side effects, and best dose of eltanexor in combination with venetoclax for the treatment of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Eltanexor works by trapping "tumor suppressing proteins" within the cell, thus causing the cancer cells to die or stop growing. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving eltanexor together with venetoclax may be safe, tolerable and/or effective in treating patients with relapsed or refractory MDS or AML.
WBC must be less than 25,000/ul prior to study start (hydroxyurea allowed).
A bone marrow aspirate must be performed, and tissue collected for entrance to the trial unless circulating blasts >/= 5% in which case, peripheral blood can be used.
Eastern Cooperative Oncology Group Performance Status of 0 - 2.
Anticancer therapy, including investigational agents </= 2 weeks or </= 5 half-lives of the drug, whichever is shorter, prior to C1D1. (Use of hydroxyurea is permitted).
Inadequate recovery from toxicity attributed to prior anti-cancer therapy to </= Grade 1 (NCI CTCAE v5.0), excluding alopecia or fatigue.
Prior treatment with SINE compounds or other inhibitors of XPO1.
History of allogeneic hematopoietic stem cell transplant (HCT), or other cellular therapy product, within 3 months.
Single group
Eltanexor
DrugEltanexor will be taken by mouth
Venetoclax
DrugVenetoclax will be taken by mouth
Bone Marrow Aspiration and Biopsy
Procedure/SurgeryUndergo bone marrow aspiration and biopsy
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Incidence of adverse events
Adverse medical events will be tabulated and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Biologically effective dose (BED) of eltanexor in combination with venetoclax
Measured by complete remission
Complete remission
By 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
Overall response rate
By 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
Progression free survival
Will be estimated using the method of Kaplan and Meier accompanied by 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
Overall survival
Will be estimated using the method of Kaplan and Meier accompanied by 95% (e.g. based on standard Gaussian methods or bootstrap methods, as appropriate) confidence intervals.
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Vanderbilt-Ingram Cancer Center
Lead sponsor
Karyopharm Therapeutics Inc
Collaborator
National Cancer Institute (NCI)
Collaborator
