A Phase 1 Trial of 8-Chloro-Adenosine in Combination With Venetoclax in Patients With Relapsed/Refractory Acute Myeloid Leukemia
This phase I trial tests the safety, side effects, and best dose of a new 8-chloroadenosine in combination with venetoclax in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory). 8-Chloroadenosine may help block the formation of growths that may become cancer. 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 8-chloroadenosine in combination with venetoclax may help prevent the disease from coming back in patients with acute myeloid leukemia.
• Documented informed consent of the participant and/or legally authorized representative.
• Age: \>= 18 years.
• Eastern Cooperative Oncology Group (ECOG) =\< 2.
• Life expectancy \> 3 months.
• Patients with histologically confirmed acute myeloid leukemia (AML), according to World Health Organization (WHO) criteria, with relapsed/refractory disease.
• Patients must have any one of the following treatment history criteria:
‣ Relapsed AML
• Failed at least 1 line of salvage therapy or
∙ Untreated relapse and are not candidates for allogeneic hematopoietic stem cell transplantation (alloHCT)
⁃ De novo AML
• have not achieved complete response (CR) after 2 lines of therapy or
∙ refractory to frontline therapy and not eligible for alloHCT
⁃ AML evolving from myelodysplastic syndrome (MDS) or myeloproliferative disorder who have failed hypomethylating agents (HMA) or induction chemotherapy
⁃ Patients who have relapsed after allo-HCT are eligible if they are at least 3 months after HCT, do not have active graft versus host disease (GVHD) and are off immunosuppression except for maintenance dose of steroids (prednisone 10 mg/day or less).
• Male subjects must agree to not donate sperm while taking protocol therapy through at least 90 days after the last dose.
• White blood cell (WBC) =\< 25 x 10\^9/L prior to initiation of venetoclax. Cytoreduction with hydroxyurea prior to treatment and/or during cycle 1 may be required.
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease).
• Aspartate aminotransferase (AST) =\< 2.5 x ULN.
• Alanine aminotransferase (ALT) =\< 2.5 x ULN.
• Creatinine clearance of \>= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula.
• QTc =\< 480 ms.
• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months (females) and 3 months (males) after the last dose of protocol therapy.
‣ Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only).