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OncoMatch/Clinical Trials/NCT05442216

Tagraxofusp and Azacitidine With Venetoclax in Newly Diagnosed Secondary AML After Hypomethylating Agents

Is NCT05442216 recruiting? Yes, currently enrolling (May 2026). This Phase 2 trial studies multiple treatments including Tagraxofusp and Azacitidine for acute myeloid leukemia.

Phase 2RecruitingJoshua ZeidnerNCT05442216Data as of May 2026

Treatment: Tagraxofusp · Azacitidine · VenetoclaxA treatment cycle is 28 days. Tagraxofusp will be administered at 9 mcg/kg IV over 15 minutes (-5 or +15 minutes) daily for 3 consecutive days (or 3 doses over a period not to exceed 10 days if postponement is required to allow for toxicity resolution), followed by azacitidine administered at 75 mg/m2 SQ or IV daily on Day 4 through Day 10. Venetoclax will begin on Day 4 and continue through Day 24 (21 consecutive days). A bone marrow biopsy (BM Bx) will be performed on Day 24 (+3 days) of Cycle 1. Subjects who do not achieve a CRm will proceed with the next cycle of Induction Phase study treatment, irrespective of hematologic laboratory values. Cycle 2+ will consist of tagraxofusp 9 mcg/kg IV over 15 minutes daily for 3 consecutive days (Day 1-3 or 3 doses over a period not to exceed 10 days if postponement is required to allow for toxicity resolution), azacitidine 75 mg/m2 SQ or IV on Day 1 through Day 7 or Days 1-7 or 1-5, 8-9 and venetoclax 400 mg daily Day 1 through Day 21. A bone marrow biopsy (BM Bx) will be performed on Day 21 (+3 days) of Cycle 2. If a CRm is obtained or maintained, the subject will move to or remain on the Continuation Phase. Subjects who do not achieve a marrow CR (CRm) after Cycle 2 will proceed with the next cycle of Induction Phase study treatment as described above, irrespective of hematologic laboratory values. If a CRm is obtained after Cycle 3 or 4, the subject will move to the Continuation Phase . If a CRm is not obtained after Cycle 4, study treatment will be discontinued and the subject will move to follow up. If per the investigator, the subject is receiving clinical benefit, study treatment may continue until toxicity or completion of 12 total cycles. A BM Bx will be performed at least every 3 cycles for these subjects.

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Extracted eligibility criteria

Cancer type

Acute Myeloid Leukemia

Biomarker criteria

Required: IL3RA overexpression (CD123 positivity on leukemia cells by centralized flow cytometry)

Subjects must have documented CD123 positivity on leukemia cells by a centralized flow cytometry assay (Hematologics).

Performance status

ECOG 0–2(Ambulatory, capable of self-care)

Prior therapy

No prior treatment (treatment-naive required)

Must have received: hypomethylating agent (azacitidine, decitabine, oral decitabine/cedazuridine) — for MDS, CMML, MDS/MPN overlap syndromes, or MPN's

Subjects must have received at least 2 cycles of hypomethylating agents (azacitidine or decitabine or oral decitabine/cedazuridine) for the management of MDS, CMML, MDS/MPN overlap syndromes, or MPN's.

Cannot have received: tagraxofusp (tagraxofusp)

Previous receipt of tagraxofusp.

Cannot have received: chemotherapy

Exception: hydroxyurea, leukapheresis and/or cyclophosphamide allowed prior to study entry per protocol

Treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of registration. NOTE: hydroxyurea, leukapheresis and/or cyclophosphamide are allowed prior to study entry per the protocol.

Cannot have received: biologic therapy

Treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of registration.

Cannot have received: wide-field radiation

Treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of registration.

Cannot have received: investigational drug

Treatment with investigational drug within 21 days of registration.

Cannot have received: allogeneic stem cell transplant

Previous allogeneic stem cell transplant within 60 days prior to registration.

Lab requirements

Blood counts

Demonstrate adequate organ function within 28 days prior to registration.

Kidney function

Demonstrate adequate organ function within 28 days prior to registration.

Liver function

Demonstrate adequate organ function within 28 days prior to registration.

Cardiac function

Left ventricular ejection fraction (LVEF) ≥ 45%. No uncontrolled CHF, cardiac insufficiency Grade III or IV (NYHA), uncontrolled angina/hypertension/arrhythmia, significant ECG abnormalities, or history of MI/stroke within 6 months.

Demonstrate adequate organ function within 28 days prior to registration. Left ventricular ejection fraction (LVEF) ≥ 45%. Clinically significant cardiovascular disease including: Uncontrolled CHF, Cardiac insufficiency Grade III or IV per New York Heart Association (NYHA) classification, Uncontrolled angina/hypertension/arrhythmia, Clinically significant abnormalities on a 12-lead electrocardiogram, History of myocardial infarction or stroke within 6 months of registration.

Structured fields extracted by AI. May contain errors — verify against the official protocol.

US trial sites

  • University of Miami · Miami, Florida
  • AdventHealth Orlando · Orlando, Florida
  • Roswell Park Cancer Institute · Buffalo, New York
  • University of North Carolina at Chapel Hill · Chapel Hill, North Carolina
  • Atrium Health Wake Forest Baptist Comprehensive Cancer Center · Winston-Salem, North Carolina

Showing up to 5 US sites. See all sites on ClinicalTrials.gov →

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