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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—navitoclax, venetoclax, and decitabine (a chemotherapy drug)—to determine the optimal dose and understand the side effects in treating acute myeloid leukemia (AML). It targets individuals whose AML has returned or isn't responding to other treatments, particularly those who have already tried venetoclax without success. Participants should have AML that persists despite prior treatment and must be able to swallow pills. The trial aims to assess how effectively these drugs work together to stop cancer cells from growing or spreading. As a Phase 1 trial, the research focuses on understanding how the treatment functions in people.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of navitoclax, venetoclax, and decitabine has been tested for safety in patients with acute myeloid leukemia (AML). In a study with patients who had received many previous treatments, early results suggested that this combination might be safe, but more information is needed to confirm this. Other studies indicate that venetoclax and decitabine together are generally well-tolerated in older AML patients, showing promising safety results. However, since this is a Phase 1 trial, the main goal is to find the best dose and check for side effects, which means there could still be unknown risks. Participants should consider these findings when deciding whether to join a trial involving these drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of navitoclax, venetoclax, and decitabine for treating acute myeloid leukemia (AML) because it targets cancer cells in a unique way. While standard treatments often include chemotherapy, this combo specifically inhibits proteins that help cancer cells survive, potentially leading to more effective destruction of the cancer. Additionally, using these drugs together may enhance their cancer-fighting abilities, offering a new hope for patients who don't respond well to traditional therapies. This approach could bring a powerful new option to the table, aiming for better outcomes with possibly fewer side effects.

What evidence suggests that this treatment might be an effective treatment for acute myeloid leukemia?

This trial will evaluate the combination of navitoclax, venetoclax, and decitabine for treating acute myeloid leukemia (AML). Research has shown that this combination may help treat AML, especially when the disease returns or doesn't respond to other treatments. In one study, about 20% of patients achieved complete remission, with no signs of cancer, after using this combination. Previous patients, particularly older adults with AML, have experienced positive results with venetoclax and decitabine. These drugs stop cancer cells from growing and dividing. While more research is needed, early findings suggest this combination could be effective for difficult-to-treat AML. ^{1 2 3 4 6}

Who Is on the Research Team?

Anthony Stein, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4264/533524/Phase-1-Trial-of-Navitoclax-Venetoclax-Decitabine

Phase 1 Trial of Navitoclax/Venetoclax/Decitabine ... Participants received a median of 2 cycles of treatment (range: 1-5 cycles). Three pts (20%), one from each DL, achieved complete remission (CR) ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124070228

Phase 1 Trial of Navitoclax/Venetoclax/Decitabine ... This was a single-center phase 1 study to investigate the safety and preliminary efficacy of the addition of NAV to the regimen of VEN and decitabine (DEC) in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12241227/

The efficacy and safety of venetoclax combined with ... Several studies have confirmed that combination strategies of VEN and DEC have obtained positive results in the treatment of elderly patients ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05455294

NCT05455294 | Combination Navitoclax, Venetoclax and ... The purpose of this research study is to test the safety of a new three drug combination of navitoclax, decitabine, and venetoclax to treat advanced myeloid ...

5. nature.com nature.com/articles/s41375-025-02730-3

Outcomes of patients treated with venetoclax plus ... The 5-year relative survival of patients with AML is ~32%, and survival rates are dependent on age at diagnosis. Patients <50 years of age have ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40632299/

The efficacy and safety of venetoclax combined with ... Our findings demonstrated that the VEN + DEC regimen is both effective and safe for treating elderly patients with AML.