A Phase 1B Investigator Initiated Study of Safety and Tolerability of Dexamethasone (D) in Combination With Venetoclax-based Low-Intensity Therapy (LIT) in Treatment-Naïve Acute Myeloid Leukemia (AML): DLIT-AML

NCT07014462 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00003614/UVMC2503
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study is investigating whether adding dexamethasone, an anti-inflammatory medication, to a standard venetoclax-based low-intensity therapy (LIT) is safe and well-tolerated in patients with newly diagnosed Acute Myeloid Leukemia (AML) who are not eligible for intensive chemotherapy. Study Goals Primary Goal: To assess the safety and tolerability of dexamethasone in combination with venetoclax-based LIT. Secondary Goal: To evaluate how this treatment affects patients' quality of life using surveys. Exploratory Goal: To measure the treatment response, including remission rates and signs of minimal residual disease. What Happens in the Study? Patients will receive treatment over six cycles. Dexamethasone is given in different doses during the first six cycles along with venetoclax and another standard chemotherapy drug.

Conditions

AML - Acute Myeloid Leukemia

Keywords

AML; Dexamethasone; Venetoclax-

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of adding dexamethasone to venetoclax-based low-intensity therapy in treatment-naïve AML patients

  The primary outcome will assess the safety and tolerability of the combined regimen. This will include the incidence and severity of adverse events (AEs) graded by NCI CTCAE v5.0, with special attention to clinically significant non-hematologic grade 4 AEs during the first 2 cycles. Overall AE frequency, organ system affected, and hematologic vs. non-hematologic classification will be recorded. Short-term toxicity will be reviewed after enrollment of the first 8-10 patients to determine feasibility for continued accrual.

  From start of treatment through completion of 6 cycles (each cycle is 28 days; approximately 6 months total)

Study Arms (1)

Adults with ND-AML

EXPERIMENTAL

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.

Drug: Dexamethasone plus Venetoclax-based Low-Intensity Therapy

Interventions

Dexamethasone plus Venetoclax-based Low-Intensity Therapy DRUG

Participants will receive standard low-intensity therapy (LIT) regimens for newly diagnosed AML, which may include venetoclax combined with either azacitidine, decitabine, or low-dose cytarabine, per treating physician's discretion. In addition, participants will receive dexamethasone administered orally at 10 mg twice daily on days 1-3 of cycles 1 and 2, and 20 mg orally on day 1 of cycles 3 through 6. This intervention is being studied to evaluate whether the addition of dexamethasone improves tolerability and clinical outcomes in patients unfit for intensive chemotherapy.

Adults with ND-AML

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• ECOG performance status ≤2
• Newly diagnosed AML morphologically confirmed in a bone marrow biopsy and aspiration done within 2 months of study enrollment, following the WHO 2022 morphologic classification for myeloid malignancies9
• No prior AML treatment (treatment-naïve)
• Ineligibility or unwillingness to undergo high-dose chemotherapy induction. Patient candidacy for high dose intensive chemotherapy or ineligibility due to older age or unfit medical status will be determined by the primary treating physician.
• Adequate renal function including creatinine clearance \> 30 ml/min based on the Cockcroft-Gault equation
• Normal liver function with direct bilirubin ≤ 2xULN, ALT and AST ≤ 3xULN, unless deemed to be related to underlying leukemia
• Women of child-bearing potential and men (except if previous vasectomy) must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Men must agree to use a condom and not father a child or donate sperm for the duration of the study and for 90 days after completion of therapy
• A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
• Patients with known previous exposure to HMA or LDAC for treatment of a pre-leukemic condition including myelodysplastic syndromes or myeloproliferative neoplasms are eligible.

You may not qualify if:

• Acute promyelocytic leukemia diagnosis
• Bone marrow transplant expected after first or second cycle of venetoclax-based LIT.
• White Blood Cell (WBC) count \>25K. If WBC is \>25K in an otherwise eligible patient, the use of cytoreduction is allowed and patients can be included when WBC \<25K. Hydroxyurea (at any dose) and/or one dose of cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy
• The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions: 1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia, or 2) cytoreduction as point 3.2.3.
• Patients with any concurrent uncontrolled clinically significant medical condition, laboratory abnormality, or psychiatric illness, which could place the patient at unacceptable risk of study treatment.
• Baseline high-dose steroid treatment at dose preceding AML diagnosis for any cause, including concomitant autoimmune disease. The maximum acceptable daily steroid dose is the equivalent of 5 mg of prednisone.
• Adrenal insufficiency
• Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known uncontrolled HIV infection. Patients with a history of treated HBV or HCV which has been previously treated, or those with controlled HIV on treatment are eligible.
• Patients receiving any other investigational agents
• Pregnant or nursing patients
• Patients with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications
• Patients with uncontrolled diabetes, defined as hemoglobin A1C (HgbA1C) levels \>9 and significant baseline hyperglycemia. Patients with controlled diabetes are eligible provided they continue with their treatments and HgbA1C is monitored every 3 months. HgbA1C levels are required only in diabetic patients riteria:

Sponsors & Collaborators

• University of Vermont: lead

Study Sites (1)

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: June 11, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)