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

NCT05442216 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN AML20-472
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 7

Brief Summary

A 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.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Complete Response

  The CR rate based on ELN AML response criteria in subjects with newly diagnosed AML with p-HMA receiving tagraxofusp and azacitidine and venetoclax

  5 years

Secondary Outcomes (9)

• Assess adverse events

  4 months

• Rate of CR + CRh

  5 years

• Rate of CR without evidence of Minimal Residual Disease (MRD)

  5 years

• Overall Response Rate (ORR)

  5 years

• Overall Survival (OS)

  5 years

Study Arms (1)

Experimental Group

EXPERIMENTAL

Each treatment cycle will last 28 days. For Cycle 1, tagraxofusp 9 mcg/kg IV over 15 minutes daily for 3 consecutive days followed by azacitidine administered at 75 mg/m2 SQ or IV daily on Day 4 through Day 10. Venetoclax with ramp-up dosing on Day 4 through Day 24. A bone marrow biopsy (BM Bx) will be performed on Day 24 (+3 days) of Cycle 1. If a CRm is obtained, the subject will move to the Continuation Phase. Subjects who do not achieve a CRm will proceed with the next cycle of Induction Phase study treatment. Cycle 2+ will consist of tagraxofusp 9 mcg/kg IV over 15 minutes daily (Day 1-3), 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. 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. If a CRm is not obtained after Cycle 4, study treatment will be discontinued and the subject will move to follow up

Drug: Tagraxofusp; Drug: Azacitidine; Drug: Venetoclax

Interventions

Tagraxofusp DRUG

9 mcg/kg intravenously Days 1-3

Experimental Group

Azacitidine DRUG

75 mg/m2 subcutaneously or intravenously Days 1-7

Experimental Group

Venetoclax DRUG

400 mg daily Days 1-21.

Experimental Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Subjects must have newly diagnosed, untreated AML, as defined by ≥ 20% blasts in peripheral blood or bone marrow by manual aspirate differential, immunohistochemistry staining, or flow cytometry, as defined by standard WHO 2016 diagnostic criteria.
• Subjects must have documented CD123 positivity on leukemia cells by a centralized flow cytometry assay (Hematologics).
• Documented diagnosis of prior MDS, CMML, MDS/MPN overlap syndromes, or MPN's according to WHO criteria. 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. NOTE: Subjects who have enrolled on clinical trials with investigational agents in combination with HMA's will still be eligible. Investigational agents must have been discontinued \>14 days prior to study treatment initiation. Subjects who have enrolled on clinical trials with investigational agents in combination with HMA's will still be eligible. Investigational agents must have been discontinued \> 21 days prior to study treatment initiation.
• WBC \< 30 x 109 /µL- subjects with WBC ≥ 30 x 109 /µL may still be eligible after receiving cytoreduction measures such as hydroxyurea, and/or leukapheresis, if WBC \< 30 x 109 /µL prior to study treatment initiation. Cytoreduction with hydroxyurea, leukapheresis and/or cyclophosphamide is allowed prior to treatment. Hydroxyurea must be discontinued ≥ 12 hours prior to study treatment initiation. Cyclophosphamide must be discontinued ≥ 5 days prior to study treatment initiation.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2.
• Demonstrate adequate organ function within 28 days prior to registration.
• Left ventricular ejection fraction (LVEF) ≥ 45%.
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
• Females of childbearing potential and male participants must be willing to use effective contraception as outlined in the protocol.
• Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• Patients with known evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Subjects who are suitable for and are willing to receive intensive chemotherapy.
• Diagnosis of acute promyelocytic leukemia.
• Known CNS involvement with AML.
• Previous receipt of tagraxofusp.
• 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.
• Treatment with investigational drug within 21 days of registration.
• Previous allogeneic stem cell transplant within 60 days prior to registration.
• Receiving immunosuppression therapy, with the exception of prednisone ≤ 10mg/d, for the treatment or prophylaxis of GVHD. If the patient has been on immunosuppressant treatment or prophylaxis for GVHD, the treatment must have been discontinued at least 14 days prior to study treatment initiation and there must be no evidence of Grade ≥ 2 GVHD.
• History of other malignancies (excluding MDS, CMML, MDS/MPN, MPN's) within 2 years prior to reigstration, with the exception of: adequately treated in situ carcinoma of the cervix, breast, prostate; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. Subjects receiving maintenance or adjuvant therapy for organ-confined malignancy such as breast or prostate cancer are eligible. Maintenance and/or adjuvant chemotherapy must be discontinued \>72 hours prior to study treatment initiation. Those with substantial potential for recurrence and/or ongoing active malignancy must be discussed with the sponsor-investigator before registration.
• 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

Sponsors & Collaborators

• Joshua Zeidner: lead
• Stemline Therapeutics, Inc.: collaborator
• University of North Carolina, Chapel Hill: collaborator

Study Sites (7)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

AdventHealth Orlando

Orlando, Florida, 32803, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Penn Medicine Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Lifespan Health System Rhode Island Hospital

Providence, Rhode Island, 46278, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

tagraxofusp; Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Joshua Zeidner, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua Zeidner, MD

CONTACT

732-236-3903; joshua_zeidner@med.unc.edu

LeaEtta Hyer

CONTACT

317-634-5842; lhyer@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: June 28, 2022
• First Posted: July 1, 2022
• Study Start: May 1, 2024
• Primary Completion (Estimated): July 21, 2030
• Study Completion (Estimated): July 21, 2031
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)