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Anti-tumor antibiotic

Mitoxantrone for Acute Myeloid Leukemia

Phase 1

Recruiting

Led By Andrew Kent, MD, PhD

Research Sponsored by University of Colorado, Denver

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Subject must have adequate liver function as demonstrated by: AST ≤ 3.0 × ULN, ALT ≤ 3.0 × ULN, bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome.

Subject must have confirmation of non-APL AML by WHO criteria and have been treated with first-line venetoclax/HMA (azacitidine or decitabine).

Must not have

Any prior exposure to an anthracycline or anthracenedione.

Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Uncontrolled is defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is for patients with a type of blood cancer called AML who have not responded well to initial treatment. The study will test different doses of a new drug in a small group of patients before

Who is the study for?

This trial is for adults with Acute Myeloid Leukemia (AML) who didn't respond to initial treatment with Venetoclax+HMA or those in remission but still have detectable disease. Key eligibility details are not provided, so interested individuals should inquire further.

What is being tested?

The study tests Mitoxantrone's effectiveness on AML that's resistant to Venetoclax. It starts with dose-finding and then expands into three groups to assess safety and efficacy more broadly.

What are the potential side effects?

Mitoxantrone can cause side effects like heart damage, lowered blood cell counts increasing infection risk, nausea, hair loss, and mouth sores. Azacitidine may add risks of anemia and bleeding.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My liver functions are within normal limits, except for Gilbert's syndrome.

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I have AML (not APL type) and was treated with venetoclax and HMA.

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My condition did not improve after at least one full treatment cycle with venetoclax/HMA.

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I can take care of myself and am up and about more than half of my waking hours.

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My kidneys are functioning well, with a creatinine clearance rate of 60 mL/min or higher.

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My heart is strong, with an ejection fraction over 50%.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with anthracycline or anthracenedione before.

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I have an infection that hasn't improved with treatment.

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My leukemia has spread to my brain or spinal cord.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum tolerated dose (MTD)

Number of grade 4 or 5 adverse events

Overall response rate

Secondary study objectives

Number of conversions from MRD+ to MRD-

Survival data

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort 4Experimental Treatment3 Interventions

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.

Group II: Cohort 3Experimental Treatment3 Interventions

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.

Group III: Cohort 2Experimental Treatment3 Interventions

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.

Group IV: Cohort 1Experimental Treatment3 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Azacitidine

2012

Completed Phase 3

~1440

Mitoxantrone

2008

Completed Phase 3

~1550