Health TrialsbyHealthPanel

Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia

ConditionsLeukemiaMyeloid LeukemiaMonocytic Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-80
SponsorUniversity of Colorado, Denver

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Subject must have relapsed disease per IWG criteria or disease refractory to first line venetoclax/HMA defined by less than a PR response after ≥ 1 complete cycle of venetoclax/HMA.

Subject must have either measurable residual disease (MRD+), as measured by FDA-approved flow cytometric test performed by Hematologics (cohort 3 and 4) or relapsed/refractory disease (cohort 1 and 2).

Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of ≤ 2.

Disqualifiers

Subject has known active CNS involvement from AML.

Significant active cardiac disease within the previous 6 months including: New York Heart Association heart failure > class 2, unstable angina, or myocardial infarction.

Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.

Subject has a malabsorption syndrome or other condition that precludes enteral route of administration. This includes history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), celiac disease (e.g.

Trial design

Design model

Sequential

Treatments tested in this trial

  • 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.

Treatment groups

30 Participants
are divided into 4 treatment groups
Group A: Cohort 1Experimental treatment 3 interventions
Group B: Cohort 2Experimental treatment 3 interventions
Group C: Cohort 3Experimental treatment 3 interventions
Group D: Cohort 4Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Maximum tolerated dose (MTD)

Cohort 1: Determine the maximum tolerated (MTD) and/or recommended phase 2 dose (RP2D) of mitoxantrone in combination with venetoclax+azacitidine.

Time frame
Reassessment at end of each cycle (28 days) until MTD reached, up to 5 cycles total if needed
2

Overall response rate

Cohort 2: Overall response rate (CR+CRi+PR+MLFS) after treatment with mitoxantrone and venetoclax+azacitidine

Time frame
Baseline to End of Treatment (up to 1 year)
3

Number of grade 4 or 5 adverse events

Cohorts 3 and 4: determine the safety of mitoxantrone in combination or in sequence with standard of care venetoclax+azacitidine

Time frame
Baseline to End of Treatment (up to 1 year)

Secondary outcomes

1

Survival data

All cohorts: Relapse free survival, remission duration, overall survival and adverse events by grade and attribution

Time frame
Through study completion, up to 5 years
2

Number of conversions from MRD+ to MRD-

Cohorts 3 and 4: Determine the rate of conversion from MRD+ to MRD- after treatment with mitoxantrone.

Time frame
After each cycle of treatment (28 days), up to 3 cycles total

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Colorado, Denver

Lead sponsor

The Leukemia and Lymphoma Society

Collaborator

Source ClinicalTrials.gov
Apply now