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Navtemadlin + Decitabine for Acute Myeloid Leukemia

Phase 1

Waitlist Available

Led By Kevin R Kelly

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have measurable disease as defined the presence of >= 20% blasts in bone marrow or extramedullary leukemia

Relapsed/refractory AML (>= 5% blasts in bone marrow or extramedullary leukemia); adverse cytogenetics, e.g., as defined by the Medical Research Council (MRC) Prognostic Groupings; secondary AML; organ dysfunction arising from significant co-morbidities not directly linked to leukemia; Eastern Cooperative Oncology Group [ECOG] = 2) or not willing to undergo intensive chemotherapy

Must not have

History of allergic reactions attributed to compounds of similar chemical or biologic composition to KRT-232 (AMG-232) or decitabine

Patients with previously untreated AML with core binding factor (CBF) chromosomal aberrations (inv[16]/t[16;16] or t[8;21]); Note that patients with relapsed or refractory AML with CBF chromosomal aberrations will be eligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, 1, 3, 5, 8 and 24 hours post dose on days 4 and 18 of course 1; baseline, 0.5 hour, prior to end of infusion, 0.25, 0.5, and 1 hour post infusion on days 1 and 4 of course 1

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing navtemadlin + decitabine to treat patients with AML that has come back, does not respond to treatment, or is newly diagnosed. Navtemadlin blocks enzymes needed for cell growth. Decitabine works in different ways to stop the growth of cancer cells. Giving navtemadlin and decitabine together may work better than decitabine alone.

Who is the study for?

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).

What is being tested?

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.

What are the potential side effects?

Possible side effects include reactions at enzyme blocking sites which may affect cell growth elsewhere in the body, typical chemotherapy-related issues like nausea and fatigue, potential impact on blood counts leading to increased infection risk, as well as organ-specific inflammation.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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I am 18 years old or older.

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

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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My AML is untreated or relapsed with specific genetic changes.

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I have a history of unusual bleeding.

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

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

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

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

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

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, 1, 3, 5, 8 and 24 hours post dose on days 4 and 18 of course 1; baseline, 0.5 hour, prior to end of infusion, 0.25, 0.5, and 1 hour post infusion on days 1 and 4 of course 1

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, 1, 3, 5, 8 and 24 hours post dose on days 4 and 18 of course 1; baseline, 0.5 hour, prior to end of infusion, 0.25, 0.5, and 1 hour post infusion on days 1 and 4 of course 1

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, 1, 3, 5, 8 and 24 hours post dose on days 4 and 18 of course 1; baseline, 0.5 hour, prior to end of infusion, 0.25, 0.5, and 1 hour post infusion on days 1 and 4 of course 1 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of toxicity

Secondary study objectives

Change in p53 signaling

P53 activation

Pharmacokinetics (PK) profile

Other study objectives

Complete cytogenetic response (CRc or molecular CR [CRm])

Complete response (CR) or CR with incomplete blood count recovery

Pharmacodynamic (PD) effects on leukemia blasts

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Decitabine

2004

Completed Phase 3

~1680

Bone Marrow Biopsy

2021

Completed Phase 3

~230