Ivosidenib or Enasidenib Followed by Azacitidine Plus Venetoclax or Azacitidine Plus Venetoclax Followed by Ivosidenib or Enasidenib for the Treatment of IDH Mutated Acute Myeloid Leukemia in Older Patients. The I-DATA Study

• Status: Not yet recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This phase II study compares the order of treatment with ivosidenib or enasidenib and azacitidine plus venetoclax in treating older patients with acute myeloid leukemia with genetic changes in the IDH1 or IDH2 genes (IDH mutated). Ivosidenib is in a class of medications called isocitrate dehydrogenase-1 (IDH1) inhibitors. It works by slowing or stopping the growth of cancer cells. Enasidenib is in a class of medications called an IDH2 inhibitor. It also works by slowing or stopping the growth of cancer cells. 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. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. This study may help researchers determine which treatment order is best for older patients with IDH mutated acute myeloid leukemia: 1) ivosidenib or enasidenib followed by azacitidine plus venetoclax; or 2) azacitidine plus venetoclax followed by ivosidenib or enasidenib.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Alice Mims
• Treatments: Azacitidine; Ivosidenib; Venetoclax

Criteria

Inclusion Criteria:

• Patients >= 60 years with newly diagnosed IDH1 or IDH2 mutated AML

• Not a candidate for or refuses intensive induction therapy

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Creatinine clearance > 40 ml/min

• Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) < 5 x upper limit of normal

• Total bilirubin < 1.5 x upper limit of normal (except for patients with Gilbert's disease)

• For female patients of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the screening visit throughout the study treatment period and for 30 days following the last dose of either study drug

• For male patients of childbearing potential having intercourse with females of childbearing potential, the willingness to abstain from heterosexual intercourse or use a protocol recommended method of contraception from the start of study treatment throughout the study treatment period and for 90 days following the last dose of either study drug. Males must also refrain from sperm donation from the start of study treatment throughout the study treatment period and for 90 days following the last dose of either dose of study drug

• Willingness to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures and study restrictions

Exclusion Criteria:

• Patients with acute promyelocytic leukemia

• Known active central nervous system involvement of leukemia

• History of active non-myeloid malignancy except for the following: adequately treated local basal cell carcinoma or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease or any other cancer that has been in complete remission without treatment for >= 5 years prior to enrollment

• Evidence of ongoing uncontrolled systemic bacterial, fungal or viral infection at the time of start of study treatment

• Uncontrolled infection with hepatitis C, hepatitis B, or human immunodeficiency virus (HIV)

• Pregnancy or breast feeding

• Concurrent participation in an investigational drug trial with therapeutic intent defined as prior study therapy within 14 days prior to study treatment

• Inability to tolerate oral medications including symptomatic disease significantly affecting gastrointestinal function such as inflammatory bowel disease or resection of stomach or small bowel