Phase 1 part of the study will consist of a dose-escalation and a dose-finding component.~Phase 2 will enroll subjects AML, CLL, or MDS, into 7 groups:~Group 1: Subjects with AML or MDS having marrow blasts over > 10%, who have experienced an inadequate response or progression on venetoclax combinations with either HMAs or low dose Ara-C or similar venetoclax combinations~Group 2: Fadraciclib: Subjects with AML or MDS relapsed/refractory having marrow blasts over > 10% with FLT3, KIT, MAPK pathway (N and K RAS, BRAF, PTPN11, NF1) mutations after at least 1 line of prior therapy.~Group 3: Fadraciclib: Subjects with CLL who have progressed on 2 or more lines of therapy, including a Bruton's tyrosine kinase (BTK) inhibitor and venetoclax.~Group 4: Fadraciclib plus azacitidine: Subjects with AML or MDS who have progressed after therapy with an HMA.~Group 5: Fadraciclib plus venetoclax: Subjects with AML or MDS who have progressed after therapy with venetoclax.~Group 6: Fadraciclib plus venetoclax: Subjects with CLL or small lymphocytic lymphoma (SLL) who have progressed after therapy with venetoclax.~Group 7: Basket cohort: Leukemia types suspected to have a related mechanism of action such as MCL1, or MYC amplification/over-expression not included in previous groups
This is a 2-part, phase 1/2, open-label, multicenter study designed to evaluate the safety and efficacy of fadraciclib (formerly CYC065) administered orally BID. This study consists of Phase 1 and Phase 2 components in subjects with Leukemia or Myelodysplastic syndrome (MDS) who have progressed despite having standard therapy or for which no standard therapy exists.