Navtemadlin + Decitabine for Acute Myeloid Leukemia

Palo Alto (17 mi)

Overseen byKevin R. Kelly

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: National Cancer Institute (NCI)

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?This phase Ib trial studies the side effects and best dose of navtemadlin when given together with decitabine and venetoclax in treating patients with acute myeloid leukemia that has come back after a period of improvement (recurrent), does not respond to treatment (refractory), or is newly diagnosed. Navtemadlin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as decitabine, 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. 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 navtemadlin, decitabine, and venetoclax together may work better than decitabine alone in treating patients with acute myeloid leukemia.

Eligibility Criteria

Adults (18+) with acute myeloid leukemia that's either newly diagnosed, not responding to treatment, or has returned. They must have a specific type of gene (wild-type p53), be able to undergo certain tests, and have an acceptable level of organ function. People can't join if they're on blood thinners, have certain heart conditions or infections, are taking drugs that affect liver enzymes strongly, or if their cancer is a specific subtype (acute promyelocytic leukemia).

Inclusion Criteria

My leukemia shows more than 20% blasts in my bone marrow or outside of it.

My AML has returned or is not responding to treatment, and I can't or won't have intensive chemotherapy.

I am 18 years old or older.

I can take care of myself but may not be able to do active work.

My kidney function, measured by creatinine clearance, is adequate.

Exclusion Criteria

I am allergic to medications similar to KRT-232 or decitabine.

My AML is untreated or relapsed with specific genetic changes.

I have a history of unusual bleeding.

My leukemia is a specific type with a unique genetic feature.

I am currently taking blood thinners like warfarin or factor Xa inhibitors.

I have tested positive for chronic hepatitis B or active hepatitis C.

I have not had major surgery in the last 28 days.

I do not have cancer that has spread to my brain.

Treatment Details

The trial is testing the safety and optimal dose of KRT-232 when combined with decitabine and venetoclax in patients with acute myeloid leukemia. KRT-232 aims to block enzymes needed for cancer cell growth while the chemotherapy agents work by killing or stopping the spread of cancer cells.

1Treatment groups

Experimental Treatment

Group I: Treatment (decitabine, navtemadlin, venetoclax)Experimental Treatment6 Interventions

Patients receive decitabine IV over 1 hour on days 1-10, navtemadlin PO QD on days 1-7, and venetoclax PO QD on days 1-21. Treatment repeats every 28 days for up to 4 cycles in patients with evidence of persistent AML. Starting cycle 2, patients with no morphologic evidence of AML receive decitabine IV over 1 hour on days 1-5, navtemadlin PO QD on days 1-7, and venetoclax PO QD on days 1-14. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and biopsy, and blood sample collection throughout the trial.

Decitabine is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Dacogen for: