Navitoclax + Venetoclax + Decitabine for Acute Myeloid Leukemia

Recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: Venetoclax

Must not be taking: CYP3A4 inducers, Immunosuppressants

Disqualifiers: Stem cell transplant, CNS disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

17 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib trial is to find the side effect and best dose of navitoclax when given together with venetoclax and decitabine in treating patients with acute myeloid leukemia that has come back (relapsed) or does not respond to treatment (refractory) after previous treatment with venetoclax. Chemotherapy drugs, such as navitoclax, venetoclax, and 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.

Research Team

Anthony Stein, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for adults and adolescents (16-18 years old, weighing at least 45 kg) with acute myeloid leukemia that has not improved or returned after treatment with venetoclax. Participants must have a stable heart function, normal blood counts, liver and kidney functions within certain limits, no severe infections like HIV or hepatitis, and agree to use birth control.

Inclusion Criteria

Aspartate aminotransferase (AST) =< 3.0 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)

Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy

If in the absence of anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)

Exclusion Criteria

Hematopoietic stem cell transplant within 100 days prior to day 1 of protocol therapy

Chemotherapy, radiation therapy, biological therapy, or immunotherapy within 14 days or 5 half-lives, whichever is shorter, prior to day 1 of protocol therapy with the following exceptions:

Strong or moderate CYP3A4 inducers within 14 days prior to day 1 of protocol therapy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive venetoclax and navitoclax orally once daily, and decitabine intravenously, with treatment cycles repeating every 28 days for up to 12 cycles

12 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

1 year

Treatment Details

Interventions

• Decitabine
• Navitoclax
• Venetoclax

Trial Overview The trial is testing the safety and optimal dosage of navitoclax in combination with venetoclax and decitabine in patients whose acute myeloid leukemia has relapsed or is refractory. These drugs aim to stop cancer cells from growing by killing them or preventing their division.

Participant Groups

Group I: Treatment (navitoclax, venetoclax, decitabine) Experimental Treatment 3 Interventions

Patients receive venetoclax PO QD and navitoclax PO QD on days 1-35, and decitabine IV over 1 hour on days 8-12 of cycle 1. Starting on cycle 2, patients receive venetoclax PO QD and navitoclax PO QD on days 1-28, and decitabine IV over 1 hour on days 1-5. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Dacogen for:

• Acute myeloid leukemia
• Myelodysplastic syndromes

Approved in United States as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Canada as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Dacogen for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+