A Phase I/II Study of Venetoclax in Combination With Azacitidine in Relapsed/Refractory High-Risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
This phase I/II trial investigates the side effects and best dose of venetoclax when given together with azacitidine and to see how well it works in treating patients with high-risk myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back (relapsed) or has not responded to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax and azacitidine together may help to control myelodysplastic syndrome or chronic myelomonocytic leukemia.
• Participants with post HMA-failure high-risk MDS (Int-2 or high risk by the IPSS with overall score \>/=1.5) with excess blasts \>5% with failure defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy.
• Participants with relapsed/refractory chronic myelomonocytic leukemia (CMML) and therapy-related MDS are also eligible.
• Hydroxyurea is allowed to lower the white cell count \</= 10,000/µl prior to initiation of venetoclax.
• Adequate hepatic function including total bilirubin ≤ 2.0 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and ALT/AST ≤ 3.0 x ULN unless considered due to leukemic involvement.
• Adequate renal function as calculated using the modified Cockcroft-Gault equation of ≥ 30ml/min, OR creatinine \< 2x ULN, unless related to the disease.
• Signed written informed consent.
• Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment.
• Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment.
• Age \>/= 18 years of age.
⁃ ECOG/PS ≤2