Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia

Part of paid clinical trials in Aurora, Colorado.

Sponsor
University of Colorado, Denver
Study ID
NCT06429449
Phase
PHASE1
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 80 Years
Healthy Volunteers
Not accepted

Interventions

  • Venetoclax — DRUG
    Venetoclax attaches to a protein called Bcl-2. This protein is present in high amounts in CLL cancer cells, where it helps the cells survive for longer in the body and makes them resistant to cancer medicines. By attaching to Bcl-2 and blocking its actions, venetoclax causes the death of cancer cells and thereby slows down progression of the disease.
  • Azacitidine — DRUG
    An analog of the pyrimidine nucleoside cytidine, has effects on cell differentiation, gene expression, and deoxyribonucleic acid (DNA) synthesis and metabolism, and causes cytotoxicity.
  • Mitoxantrone — DRUG
    Mitoxantrone Injection, USP (concentrate) is a synthetic antineoplastic anthracenedione for intravenous use.

Study Details

This is an open label, phase 1 study for AML subjects with relapsed or refractory disease or subjects in morphologic remission with MRD+ after first line therapy with venetoclax+HMA. A preliminary dose-finding cohort will be followed by 3 expansion cohorts.

Key Dates

Start date
Jul 21, 2024
Status verified
Jan 2026
Primary completion
Dec 31, 2026
Completion
Nov 30, 2027

Study Design

Enrollment
30 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1
    Cohort 1 will be a conventional 3+3 dose-escalation study to determine maximum tolerated (MTD) or recommended dose of mitoxantrone when used with venetoclax+azacitidine.
  • Experimental: Cohort 2
    After establishing the MTD of mitoxantrone, an expansion cohort will open. 10 subjects refractory to first-line therapy w/venetoclax+HMA, or respond then relapse after first-line therapy w/venetoclax+HMA, will enroll in the study \& receive a subsequent cycle of venetoclax+azacitidine at the dose \& schedule being administered per the standard of care, w/the determined MTD/recommended dose of IV mitoxantrone given days 1-4. Day 28 +/- 7 days of this cycle, a bone marrow biopsy will be repeated. In the absence of a ≥50% blast reduction from baseline, the subject will discontinue the study. If a CR, CRi, MLFS or blast reduction from baseline of ≥50% occurs, the subject can continue sequential cycles of venetoclax+azacitidine at the dose \& schedule being administered per the standard of care, with the MTD/recommended dose of mitoxantrone on days 1-4, up to 3 cycles. No subject will receive \>3 cycles of mitoxantrone.
  • Experimental: Cohort 3
    Subjects in a morph remission w/ MRD+ after ≤3 cycles of soc ven+HMA will enroll \& receive mitox on days 1-4 at dose tbd that is below the MTD from cohort 1, concurrently w/ven+aza, at the dose \& schedule being soc admin, over a 28-day cycle. A BMBX w/ MRD assessment will be done day 28. If MRD- occurs, subseq treatment cycles will continue to admin ven+aza, at the dose \& schedule being soc admin, w/ the tbd dose of mitox on days 1-4, for max of 3 cycles. If MRD- does not occur, the next cycle may escalate the mitox dose to a level tbd \& not exceeding the MTD, w/ ven+aza at the dose \& schedule being soc admin. If MRD- occurs, subseq treatment cycles will continue to admin ven+aza, at the dose \& schedule being soc admin, with the tbd dose of IV mitox on days 1-4, for a max of 3 cycles. If MRD- does not occur, the next cycle may escalate the mitox to a level tbd \& not exceeding the MTD, w/ ven+aza at the dose \& schedule being admin per the soc. Subjects will not receive \>3 cycles.
  • Experimental: Cohort 4
    Subjects in a morphologic remission w/ MRD+ after \>3 cyc of soc ven/HMA will enroll 28-50 days after the previous ven/HMA cyc. Subjects will receive mitox IV days 1-4 at a dose tbd below the MTD from cohort 1; on day 14, the subject will start ven+aza at the dose \& schedule per the soc. On day 42, a BMBX, w/ MRD assessment, will be repeated. If MRD- occurs, subseq cyc will cont to admin ven+aza, at the dose \& schedule per the soc, with the tbd dose of IV mitox on days 1-4, for a max of 3 cyc of mitox. If MRD- does not occur, the next cyc will retain the same schedule \& may escalate the mitox to a dose level tbd \& not exceeding the MTD. If MRD- occurs, 1 add'l cyc of mitox at this dose, w/ ven+aza at the dose \& schedule per the soc, will be given. If MRD- does not occur, the next cyc will retain the same schedule \& may escalate the mitox to a level tbd \& not exceeding the MTD.

Primary Outcome Measure

Maximum tolerated dose (MTD) [ Time Frame: Reassessment at end of each cycle (28 days) until MTD reached, up to 5 cycles total if needed ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of Colorado HospitalAuroraColorado80045
Derek Schatz
[email protected]
(720) 848-0628
Andrew Kent, MD, PhD (PRINCIPAL_INVESTIGATOR)
Maria Amaya, MD (SUB_INVESTIGATOR)
Mathew Angelos, MD (SUB_INVESTIGATOR)
Steven Bair, MD (SUB_INVESTIGATOR)
Jonathan Gutman, MD (SUB_INVESTIGATOR)
Brad Haverkos, MD (SUB_INVESTIGATOR)
Jagar Jasem, MD (SUB_INVESTIGATOR)
Manali Kamdar, MD (SUB_INVESTIGATOR)
Ajay Major, MD (SUB_INVESTIGATOR)
Christine McMahon, MD (SUB_INVESTIGATOR)
Jorge Monge Urrea, MD (SUB_INVESTIGATOR)
Daniel Pollyea, MD (SUB_INVESTIGATOR)
Marc Schwartz, MD (SUB_INVESTIGATOR)
Daniel Sherbenou, MD (SUB_INVESTIGATOR)

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