Actively Recruiting
Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia
Led by University of Colorado, Denver · Updated on 2026-01-15
30
Participants Needed
1
Research Sites
47 weeks
Total Duration
On this page
Sponsors
U
University of Colorado, Denver
Lead Sponsor
T
The Leukemia and Lymphoma Society
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating mitoxantrone in combination with venetoclax and azacitidine for adults with acute myeloid leukemia (AML) who have relapsed or refractory disease, or who remain minimal residual disease positive (MRD+) after first-line treatment with venetoclax plus hypomethylating agents (HMA). This is an open-label Phase 1 study including a dose-finding phase followed by three expansion cohorts to assess the safety and appropriate dosing of mitoxantrone with these treatments. The study begins with a dose-escalation cohort to find the maximum tolerated dose (MTD) or recommended dose of mitoxantrone given intravenously on days 1 to 4 alongside standard venetoclax plus azacitidine therapy. After determining the MTD, expansion cohorts will test mitoxantrone in different patient groups, including those refractory or relapsed after first-line treatment and those in remission but MRD+. Treatment cycles last 28 days, with mitoxantrone given on days 1 to 4 and venetoclax plus azacitidine administered per standard care schedules. Participants may receive up to three cycles of mitoxantrone depending on response, with dose adjustments allowed based on bone marrow and MRD assessments. Participants will have regular evaluations including bone marrow biopsies with MRD testing at specified intervals to monitor disease status and response. Safety will be assessed by tracking adverse events and determining the MTD. The study will measure outcomes such as overall response rate and conversion from MRD positivity to negativity over up to one year, with survival followed for up to five years. Participation includes up to five cycles during dose escalation and additional cycles during expansion cohorts, with ongoing monitoring until disease progression or change in therapy.
CONDITIONS
Brief Title
Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Confirmation of non-APL AML by WHO criteria treated with first-line venetoclax/HMA (azacitidine or decitabine)
- Relapsed disease per IWG criteria or refractory to first-line venetoclax/HMA with less than partial response after at least one complete cycle
- Measurable residual disease (MRD+) for cohorts 3 and 4, or relapsed/refractory disease for cohorts 1 and 2
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
- Adequate kidney function with creatinine clearance of 60 mL/min or higher (CKD-EPI formula)
- Adequate heart function with left ventricular ejection fraction (LVEF) above 50%, assessed within 1 month prior to study
- Adequate liver function with AST and ALT less than or equal to 3 times upper limit of normal, and bilirubin less than or equal to 1.5 times upper limit unless due to Gilbert's syndrome or leukemic involvement
- Non-sterile males must use contraception during and up to 90 days after study drug; sterile males or partners who are postmenopausal or permanently sterile are exempt
- Female participants must be postmenopausal, permanently surgically sterile, or use contraception during and for 6 months after study
- Voluntary informed consent signed prior to research procedures
You will not qualify if you...
- Active central nervous system involvement from AML
- Significant active cardiac disease in past 6 months including NYHA heart failure class greater than 2, unstable angina, or recent myocardial infarction
- Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorders unrelated to leukemia
- Malabsorption syndromes or gastrointestinal conditions affecting drug absorption like inflammatory bowel disease, celiac disease, or previous bowel surgery
- Uncontrolled systemic infections requiring therapy without improvement
- History of other malignancies except certain treated in situ carcinomas, basal or squamous cell skin cancers, prostate cancer under hormonal therapy, or previous malignancies treated with curative intent
- White blood cell count above 25 x 10^9/L (hydroxyurea or apheresis allowed for cohort 3)
- Pregnant or breastfeeding females
- Known or suspected allergies to azacitidine or mannitol
- Any prior exposure to anthracyclines or anthracenediones
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 28-day cycles until maximum 3 cycles of mitoxantrone or discontinuation
Participants receive mitoxantrone intravenously on days 1-4 combined with venetoclax and azacitidine according to the standard of care schedule. This includes dose escalation or dose determination of mitoxantrone, followed by up to 3 total cycles depending on response and cohort assignment.
1 visit per cycle for mitoxantrone administration plus additional bone marrow biopsy visits per cycle
Duration - Up to 5 years until disease progression or change in therapy
After completing mitoxantrone cycles, participants continue to have bone marrow biopsies with MRD assessments every 6 months to monitor disease status until progression or change in therapy.
Bone marrow biopsies every 6 months
Trial Site Locations
Total: 1 location
1
University of Colorado Hospital
Aurora, Colorado, United States, 80045
Actively Recruiting
Research Team
D
Derek Schatz
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
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