Tagraxofusp to Eradicate Measurable Residual Disease in Patients With Acute Myeloid Leukemia

NCT05720988 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 21-001115NCI-2021-12912
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This phase Ib/II trial tests the safety of tagraxofusp when given with or without azacitidine in patients with acute myeloid leukemia in remission with measurable residual disease who will undergo allogeneic hematopoietic cell transplant. Tagraxofusp is a recombinant protein consisting of IL-3 conjugated to a truncated diptheria toxin. The IL-3 attaches to the cancer cells and the toxic substance kills them. Azacitidine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Tagraxofusp and azacitidine may work better to kill cancer cells and eradicate measurable residual disease in patients with acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  Grade \>= 3 toxicity using Common Terminology Criteria for Adverse Events version 5.0 or severe persistent hematologic toxicity defined as absolute neutrophil count (ANC) \< 500/uL OR platelet count \< 10,000/uL in participants that have morphologic leukemia-free state (bone marrow blasts \< 5%) are conditions for a dose limiting toxicity.

  Up to 42 days

Secondary Outcomes (7)

• Measurable residual disease (MRD)

  At the end of cycle 1 and cycle 2 (each cycle is 28 days).

• MRD

  Within 30 days prior to initiation of transplant conditioning regimen and at day 100 after transplant

• Number of days between investigational regimen day 28 and initiation of transplant conditioning regimen

  Between investigational regimen day 28 and initiation of transplant conditioning regimen, through study completion, an average of 1 year.

• Rate of sinusoidal obstruction syndrome

  up to 1 year following investigational therapy

• Relapse

  Up to 1 year

Other Outcomes (2)

• CD123 expression via immunohistochemical stain on leukemia blasts in the bone marrow specimen

  at time of diagnosis or relapse and following cycle 1 and cycle 2 (each cycle is 28 days).

• T-cell (CD3) chimerism via short tandem repeat assay

  30, 90, 180, and 365 days after transplant

Study Arms (2)

Cohort I (tagraxofusp-erzs)

ACTIVE COMPARATOR

Patients receive tagraxofusp-erzs IV QD over 15 minutes on days 1-5. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Tagraxofusp-erzs

Cohort II (azacitidine, tagraxofusp-erzs)

EXPERIMENTAL

Patients receive azacitidine SC daily on days 1-5 and tagraxofusp-erzs IV QD over 15 minutes on days 8-12. Treatment repeats every 28-42 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Biological: Tagraxofusp-erzs

Interventions

Azacitidine DRUG

Given SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Cohort II (azacitidine, tagraxofusp-erzs)

Tagraxofusp-erzs BIOLOGICAL

Given IV

Also known as: Diphtheria Toxin(388)-Interleukin-3 Fusion Protein, DT(388)-IL3 Fusion Protein, DT388IL3 fusion protein, Elzonris, IL3R-targeting Fusion Protein SL-401, SL-401, Tagraxofusp, Tagraxofusp ERZS

Cohort I (tagraxofusp-erzs); Cohort II (azacitidine, tagraxofusp-erzs)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years
• AML in first or second remission, including:
• Complete remission (CR), defined as bone marrow blasts \< 5%, absence of circulating blasts, absence of extramedullary disease, absolute neutrophil count (ANC) \>= 1,000/uL, platelet count \> 100,000/uL
• Complete remission with incomplete hematologic recovery (CRi), defined as all CR criteria except for residual neutropenia (ANC \< 1,000/uL) or residual thrombocytopenia (platelet count \< 100,000/uL)
• Morphologic leukemia-free state with adequate marrow recovery, defined as bone marrow blasts \< 5%, ANC \>= 500/uL, and platelet count \>= 20,000/uL
• Minimal residual disease positive \>= 0.01% based on MPFC
• For participants in first remission, MRD positivity at any point from time of establishing first remission onward while still in first remission
• For participants in second remission, MRD positivity at any point from time of establishing second remission onward while still in second remission
• MRD must be repeated and remain positive if additional treatment is given prior to enrollment
• CD123 positivity on flow cytometry (partial, dim, or bright) from either:
• Conventional flow cytometry on marrow specimen from time of original diagnosis or first relapse
• High-sensitivity multiparametric flow cytometry on marrow specimen from time of MRD positivity
• Eastern Cooperative Oncology Group (ECOG) 0-2
• Serum albumin level \>= 3.2 g/dL in the absence of receiving albumin infusion
• Serum total bilirubin =\< 1.5 mg/dL, unless considered due to Gilbert's disease or medication effect

You may not qualify if:

• MRD negativity \< 0.01% at screening
• Intensive AML therapy within the past 14 days, or non-intensive targeted therapy within the past 7 days
• Cord blood as donor source
• Second malignancy that would be expected to limit survival within less than 2 years
• Cardiovascular disease that would result in high risk for toxicity, including:
• Uncontrolled or New York Heart Association (NYHA) class III or VI congestive heart failure
• Recurrent or uncontrolled angina
• Unstable angina, myocardial infarction, or stroke in past 6 months
• Uncontrolled hypertension
• Arrhythmia not controlled by medication
• Left ventricular ejection fraction \< 50%
• History of coronary stent placement that requires mandatory continuation of dual antiplatelet therapy
• Uncontrolled intercurrent illness that includes but is not limited to: uncontrolled infection, disseminated intravascular coagulation, psychiatric illness/compliance issues that would limit compliance with study protocol
• Any medical condition that in the opinion of the investigator places the participant at unacceptable risk for toxicity to investigational therapy

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Stemline Therapeutics, Inc.: collaborator

Study Sites (2)

Habtemariam,Bruck

Los Angeles, California, 90095, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; tagraxofusp

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

• Caspian Oliai, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: February 9, 2023
• Study Start: August 3, 2024
• Primary Completion: August 3, 2025
• Study Completion (Estimated): August 3, 2026
• Last Updated: March 8, 2024

Record last verified: 2023-01

Locations

US (2)