Dexamethasone + Venetoclax-based Therapy for Acute Myeloid Leukemia

(DLIT-AML Trial)

Overseen By Diego Adrianzen Herrera, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Vermont

Must not be taking: Chemotherapeutic agents

Disqualifiers: Acute promyelocytic leukemia, Uncontrolled diabetes, Active peptic ulcer, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety of adding dexamethasone, a medication that reduces inflammation, to a standard treatment for Acute Myeloid Leukemia (AML). The main goal is to determine if this combination is well-tolerated by patients unable to undergo intensive chemotherapy. Participants will also contribute to understanding how the treatment might improve quality of life. This trial is suitable for adults newly diagnosed with AML who haven't received prior treatment and are not fit for high-dose chemotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it does allow certain medications like hydroxyurea and cytarabine under specific conditions. It's best to discuss your current medications with the study team to see if they are compatible with the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that patients generally tolerate the combination of dexamethasone and venetoclax well. In past studies, the side effects of these drugs together mirrored those known for each drug individually, meaning they were expected and manageable.

Higher doses of venetoclax did not lead to more severe side effects. This finding is significant because it suggests that increased drug levels do not necessarily result in more serious issues.

This combination has been used safely in conditions like multiple myeloma, providing some confidence for its use in other diseases such as acute myeloid leukemia (AML).

As this trial is in an early stage, the primary goal is to assess safety. Early-stage trials are designed to closely monitor side effects, allowing for quick management of any reactions. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for AML?

Unlike the standard of care for acute myeloid leukemia (AML), which typically involves intensive chemotherapy, dexamethasone combined with venetoclax-based therapy offers a less intense treatment approach. This combination is particularly promising for patients who aren't fit for rigorous chemotherapy, as it pairs the anti-inflammatory dexamethasone with venetoclax, a drug that targets cancer cells by inhibiting a protein called BCL-2. Researchers are excited because this approach could improve tolerability and effectiveness, offering new hope to patients who have limited options.

What evidence suggests that this treatment might be an effective treatment for Acute Myeloid Leukemia?

In this trial, participants will receive a combination of dexamethasone and venetoclax-based therapy. Research has shown that combining dexamethasone with venetoclax enhances the treatment's effectiveness in killing leukemia cells. Studies have found that this combination kills more cancer cells than venetoclax alone. When venetoclax is used with other treatments, about 54% of patients respond well. Although dexamethasone alone has limited effect against leukemia, it enhances venetoclax's efficacy. This combination is believed to be more effective because dexamethasone aids venetoclax in killing cancer cells more efficiently. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed Acute Myeloid Leukemia (AML) who can't have intensive chemotherapy. They must understand and consent to the study, have decent kidney and liver function, not be pregnant or nursing, agree to use contraception, and not have a high white blood cell count unless reduced before joining.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent

I am 18 years old or older.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

Patients receiving any other investigational agents

I have been diagnosed with acute promyelocytic leukemia.

Pregnant or nursing patients

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dexamethasone in combination with venetoclax-based low-intensity therapy over six cycles

6 months

6 cycles (28 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone

Trial Overview The trial tests if adding dexamethasone to venetoclax-based Low-Intensity Therapy (LIT) is safe for AML patients ineligible for intense chemo. It looks at safety first, then quality of life through surveys, and finally treatment response including remission rates over six cycles of therapy.

How Is the Trial Designed?

Group I: Adults with ND-AML Experimental Treatment 1 Intervention

This is a single-arm, phase 1b, investigator-initiated study evaluating the safety and tolerability of adding dexamethasone to standard venetoclax-based low-intensity therapy (LIT) regimens in treatment-naïve adult patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy induction. Participants will receive venetoclax in combination with a hypomethylating agent (azacitidine or decitabine) or low-dose cytarabine, per treating physician's choice. Dexamethasone will be administered orally at 10 mg twice daily on days 1-3 of cycles 1 and 2, and 20 mg once on day 1 of cycles 3 through 6. Treatment will continue for up to 6 cycles (28 days each). The study also includes assessments of patient-reported outcomes and exploratory efficacy endpoints.

Who Is Running the Clinical Trial?

University of Vermont

Lead Sponsor

Trials

283

Recruited

3,747,000+

Citations

1. haematologica.org haematologica.org/article/view/haematol.2024.285985

Outcome of adult acute myeloid leukemia patients with ... Treatment with venetoclax/HMA resulted in an encouraging overall response rate of 54% with a CR/CRi rate of 43.5%.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37261571/

Dexamethasone enhances venetoclax-induced apoptosis ... When AML cells were co-cultured with BM-MSCs, dexamethasone combined with venetoclax showed additional anti-tumor effect compared to venetoclax ...

3. nature.com nature.com/articles/s41408-025-01264-2

Venetoclax-based treatment combinations in relapsed ... This retrospective study evaluated the efficacy and safety of Ven-based therapies in 232 MM patients without concurrent AL amyloidosis treated at Mayo Clinic ...

4. link.springer.com link.springer.com/article/10.1007/s10637-024-01471-x

14) multiple myeloma patients | Investigational New Drugs The analysis demonstrated that adding venetoclax to Kd resulted in increased ORR, ≥VGPR and ≥ CR rates compared to the control arm. Within the ...

5. researchgate.net researchgate.net/figure/Venetoclax-and-dexamethasone-individually-or-synergistically-inhibit-the-viability-of-AML_fig1_371222536

Venetoclax and dexamethasone individually or ... Dexamethasone alone has minimal impact on AML cell viability, but in combination with venetoclax, it significantly increases venetoclax-induced apoptosis in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11625073/

Exposure-response relationships of venetoclax in ... Higher venetoclax exposures however were not associated with increased rates of Grade ≥ 3 treatment-emergent adverse events, Grade ≥ 3 ...

7. news.abbvie.com news.abbvie.com/2023-09-29-AbbVie-Presents-Results-from-Phase-3-CANOVA-Study-of-Venetoclax-in-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma

AbbVie Presents Results from Phase 3 CANOVA Study of ... The safety profile of the combination of venetoclax and dexamethasone in the trial was generally consistent with the known safety profiles ...

8. ashpublications.org ashpublications.org/blood/article/130/22/2392/36574/Promising-efficacy-and-acceptable-safety-of

Promising efficacy and acceptable safety of venetoclax plus ... ORRs of 78% and 65% were observed in patients with and without t(11;14) MM, respectively. This broader activity of venetoclax beyond t(11;14) in the combination ...

9. spandidos-publications.com spandidos-publications.com/10.3892/ol.2025.14987

Treatment outcomes and safety of reduced‑dose ... Low‐dose venetoclax combined with antifungal agents appears to be less effective than standard treatment but superior to both LDAC and the I2A5 treatment ...