A Phase I Study Investigating the Safety & Efficacy of Danvatirsen as Monotherapy Followed by Combination With Venetoclax in Patients With Relapsed/Refractory MDS & AML
This is a Phase 1 study investigating the safety and efficacy of Danvatirsen as a monotherapy followed by combination with Venetoclax in patients with relapsed/refractory myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Funding Source: FDA OOPD
• Subjects must be at least 18 years of age at the time of signing the Informed Consent Form (ICF); must voluntarily sign an ICF; and be able to meet all study requirements
• Morphologically confirmed diagnosis of AML or MDS in accordance with World Health Organization (WHO) diagnostic criteria
• Subjects with relapsed/refractory AML who are refractory or relapsed to all conventional therapy and do not have any FDA approved or standard therapeutic options \& subjects with intermediated/high/very high IPSS-R MDS who are refractory or relapsed to at least 2 cycles of hypomethylating agent based therapy (azacitidine / decitabine based) OR patients with rapid progression of disease regardless of number of cycles of therapy
• At least 3 months from Allogenic stem cell transplantation and no clinical sign of active graft vs host disease (GVHD)
• WBC must be \<25,000 cells/uL and may be reduced with hydroxyurea to reach this goal prior to study start. Hydroxyurea can be administered on trial with an increase in WBC counts at the discretion of the PI
• A bone marrow biopsy must be performed within the screening window (day-28-day-1) and tissue collected for correlative analysis for entrance to this trial. Correlative sample collection is essential on this study
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Recovery to ≤ Grade 1 or baseline for any toxicities considered to be due to prior systemic treatments, excluding alopecia
• Must have adequate hepatic and renal function as follows:
⁃ ALT (SGPT) and/or AST (SGOT) ≤ 3x upper limit of normal (ULN) or ≤ 5x ULN if considered to be leukemia related; Direct bilirubin ≤ 1.5 x ULN or ≤ 3x ULN (in patients with known Gilberts syndrome or if considered to be leukemia related)
• Serum creatinine clearance ≥ 45 mL/min/1.73 m2 either measured or calculated using standard Cockroft-Gault formula
• Subjects enrolled within childbearing ages of 18-50 years should use 2 forms of contraception while on study