Gilteritinib-Azacitidine-Venetoclax Combination Therapy in Patients With Relapsed/Refractory Leukemia

NCT07755202 | Not Yet Recruiting Phase 2

• 1 other identifier: GAVE001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if gilteritinib-azacitidine-venetoclax combination drug therapy works to treat adults with FLT3-wt acute myeloid leukemia (AML). It will also learn about the safety and efficacy of this treatment. The main question this clinical trial aims to answer are:

• Will adding gilteritinib to standard-of-care therapy azacitidine-venetoclax show be more effective in treating AML FLT3-wt patients who have previously been treated with azacitidine and/or venetoclax for their disease and have had their cancer come back (relapsed) or have stopped responding to treatment (refractory)? All participants in this trial will receive the combination therapy. Participants will be on repeated 28-day cycles, for a minimum of 2 cycles, while on the study Participants will:
• Take the gilteritinib once daily, every day
• Take azacitidine and venetoclax on days 1-7 of each cycle
• Keep a daily dose diary of the days and times they have taken their treatments
• Visit the clinic every 4 weeks for checkups and tests

Conditions

Acute Myeloid Leukemia; AML With FLT3 Mutation

Outcome Measures

Primary Outcomes (1)

• Efficacy of triplet regimen on AML FLT3-wt participants

  the ORR up to two cycles of triplet therapy. ORR is defined as the proportion of participants who achieve a CR, CRi, or MLFS after completing two cycles of the combination therapy

  From enrollment to the end of treatment at week 8

Secondary Outcomes (5)

• To assess the safety of triplet regimen based on toxicity findings

  from enrollment to one month after end of treatment at 12 weeks

• Impact of triplet regimen on measurable residual disease (MRD) in participants achieving a response

  from enrollment to one month after the end of treatment at 12 weeks

• Impact of study treatment on event-free survival (EFS)

  from enrollment to end of study closeout at 36 months

• Impact of study treatment on relapse-free survival (RFS)

  from enrollment to end of study closeout at 36 months

• Impact of study treatment on overall survival (OS) in AML FLT3-wt patients

  from enrollment to end of study closeout at 36 months

Study Arms (1)

All Participants

EXPERIMENTAL

administration of combination therapy gilteritinib-azacitidine-venetoclax on repeated 28-day cycles for a minimum of 2 cycles. Gilteritinib will be taken daily and azacitidine-venetoclax on days 1-7 of each cycle.

Combination Product: gilteritinib-azacitidine-venetoclax

Interventions

gilteritinib-azacitidine-venetoclax COMBINATION_PRODUCT

administration of combination therapy gilteritinib-azacitidine-venetoclax on repeated 28-day cycles for a minimum of 2 cycles. Gilteritinib will be taken daily and azacitidine-venetoclax on days 1-7 of each cycle.

All Participants

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 old at the time of informed consent.
• Pathologically confirmed diagnosis of AML previously treated with azacitidine and venetoclax that are azacitidine and venetoclax-refractory, defined as:
• a. Primary refractory: Defined as no complete remission (CR) or CR with incomplete recovery (CRi) following at least 2 cycles of azacitidine and venetoclax with AML blasts ≥5% in the bone marrow, or 2b. Relapsed: Defined as recurrence of AML blasts ≥5% in the bone marrow after a previous CR or CRi to azacitidine and venetoclax 3. Confirmed to be negative for FLT3- internal tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations on repeat clinical testing following their last line of therapy 4. Adequate functional status (ECOG ≤ 2) 5. Participant is willing to provide informed consent and comply with trial procedures 6. Participants of either biological sex must be able and willing to use Health-Canada approved effective contraception methods starting 2-weeks prior to trial treatment, throughout the trial, and for 6 months following the last dose of trial drugs 7. For participants of child-bearing potential (menstruation within \<2 years): negative serum pregnancy test within 14-days prior to enrollment.
• \. Not currently breastfeeding and will not breastfeed while on the trial and for at least 2 months following the last trial dose.

You may not qualify if:

• Participants are excluded from the trial if any of the following criteria apply:
• \. Diagnosis of acute promyelocytic leukemia (APL), BCR-ABL positivity, or favorable risk AML 2. Currently considered as eligible for intensive chemotherapy treatment in the opinion of the Investigator 3. Inadequate organ function, defined as: 3a. Liver function: Serum aspartate aminotransferase and alanine aminotransferase ≥ 2.5 x upper limit of normal (ULN) and total bilirubin ≥ 1.5 x ULN 3b. Renal function: estimated glomerular filtration rate of \< 30 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• c. Cardiac function: New York Heart Association (NYHA) class 3 or 4 heart failure or known history of left ventricular ejection fraction ≤ 40% or known history of prolonged QTc syndrome 4. Corrected QTc of \> 450ms that is not corrected on repeat electrocardiogram (ECG) testing 5. Active and untreated CNS leukemia 6. Active solid organ malignancy requiring treatment in the last 24 months, with the exception of: 6a. Treated nonmelanoma skin cancer 6b. Completely treated breast carcinoma that is considered cured 6c. Completely treated cervical carcinoma that is considered cured 6d. Localized breast or prostate cancer receiving androgen deprivation therapy 6e. A previously treated malignancy that is considered cured with minimal risk of recurrence 7. Extramedullary disease without concomitant marrow based disease (blasts ≤5%) 8. Uncontrolled, active infection or untreated hepatitis B, C, or HIV 9. Known allergy or intolerance to azacitidine, venetoclax, or gilteritinib 10. Any comorbidity that the investigator believes would be incompatible with safe receipt or therapy 11. Inability to comply with requirements of the trial protocol 12. Pregnancy or breastfeeding 13. Unable or unwilling to use Health Canada-approved highly effective methods of contraception (i.e., hormonal contraceptives, vasectomy, tubal ligation, or double-barrier method), or abstinence while on the trial and for at least 6 months following the last dose of trial drugs.

Sponsors & Collaborators

• Florian Kuchenbauer: lead

Study Sites (1)

Vancouver General Hospital

Vancouver, British Columbia, Canada

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Hematologist, Leukemia/BMT Program

Study Record Dates

• First Submitted: August 5, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): May 1, 2030
• Last Updated: August 10, 2026

Record last verified: 2026-08

Locations

CA (1)