Phase I/II Study of Tagraxofusp in Combination With Decitabine for Patients With Myelomonocytic/Myeloproliferative Neoplasm and High Risk Myelodysplastic Syndromes

NCT05038592 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0895NCI-2021-04293
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects, best dose, and effect of tagraxofusp and decitabine in treating patients with chronic myelomonocytic leukemia. Tagraxofusp consists of human interleukin 3 (IL3) linked to a toxic agent called DT388. IL3 attaches to IL3 receptor positive cancer cells in a targeted way and delivers DT388 to kill them. Chemotherapy drugs, such as decitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving tagraxofusp and decitabine may help to control the disease in patients with chronic myelomonocytic leukemia.

Conditions

Chronic Myelomonocytic Leukemia; Chronic Myelomonocytic Leukemia-1; Myelodysplastic/Myeloproliferative Neoplasm; Chronic Myelomonocytic Leukemia-2

Outcome Measures

Primary Outcomes (3)

• Maximum tolerable dose (Phase I)

  At end of cycle 1 (1 cycle = 28 days)

• Incidence of dose limiting toxicities (Phase I)

  Up to end of cycle 1 (1 cycle = 28 days)

• Overall response (OR) (Phase II)

  Will estimate the OR for the combination treatment along with the 95% credible interval. The association between OR rate and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.

  After 2 cycles of therapy (1 cycle = 28 days)

Study Arms (1)

Treatment (decitabine, tagraxofusp-erzs)

EXPERIMENTAL

Patients receive decitabine IV over 60 minutes on days 1-5, and tagraxofusp-erzs IV over 15 minutes on days 1-3. Cycles of decitabine repeat every 28 days in the absence of disease progression or unacceptable toxicity. Treatment with tagraxofusp-erzs repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Decitabine; Biological: Tagraxofusp-erzs

Interventions

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

Treatment (decitabine, tagraxofusp-erzs)

Decitabine DRUG

Given IV

Also known as: 5-Aza-2''-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine

Treatment (decitabine, tagraxofusp-erzs)

Eligibility Criteria

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

You may qualify if:

• The participant is ≥ 18 years old
• Diagnosis of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) according to World Health Organization (WHO) and:
• Phase 1 dose escalation portion: CMML-1 or CMML-2 by WHO or higher-risk MDS (defined as IPSS-Revised score \>3.5 or with TP53 mutations) with \>5% blasts or MDS/MPN (other than CMML) with \>5% bone marrow blasts and no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine-cedazuridine) or relapse or progression after any number of cycles
• Phase 2 dose expansion portion:
• Relapsed cohort (Cohort A): CMML-1 or CMML-2 or higher-risk MDS (defined as IPSS-Revised score \>3.5 or with TP53 mutations) with \>5% blasts or MDS/MPN (other than CMML) with \>5% bone marrow blasts by WHO and no response after 6 cycles of azacitidine, decitabine, guadecitabine or ASTX727 (decitabine-cedazuridine) or relapse or progression after any number of cycles
• Hypomethylating agents (HMA) naive cohort (Cohort B): previously untreated CMML-1 or CMML-2 and intermediate-2 or high-risk IPSS or higher-risk MDS (defined as IPSS-Revised score \>3.5 or with TP53 mutations) with \>5% blasts or MDS/MPN (other than CMML) with \>5% bone marrow blasts.
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
• Left ventricular ejection fraction (LVEF) ≥ 50% as measured by multigated acquisition scan or 2-dimensional (2-D) echocardiogram (ECHO) within 28 days prior to start of therapy and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG)
• Serum creatinine ≤ 1.5 mg/dL (or ≤ 114 umol/L)
• Serum albumin ≥ 3.2 g/dL (or ≥ 32 g/L) in the absence of receipt of (IV) albumin within the previous 72 hours
• Total Bilirubin =\< 1.5 mg/dL (or ≤ 26 umol/L)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the upper limit of normal (ULN)
• Creatine kinase (CK) ≤ 2.5 times the ULN
• If a woman of child bearing potential (WOCBP), the participant has a negative serum or urine pregnancy test within 1 week prior to tagraxofusp treatment (intervals shorter than 1 week are acceptable, if required by institutional guidelines).
• The participant has signed informed consent prior to initiation of any study-specific procedures or treatment.

You may not qualify if:

• Participants has persistent clinically significant toxicities Grade .2 from previous chemotherapy not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue).
• Participants has received treatment with chemotherapy, wide-field radiation, or biologic therapy within 14 days of study entry.
• Participants has received treatment with another investigational agent within 14 days of study entry or concurrent treatment with another investigational agent.
• Participants has previously received treatment with tagraxofusp or has a known hypersensitivity to any components of the drug product.
• Participants has clinically significant cardiovascular disease (e.g., uncontrolled or any New York Heart Association Class 3 or 4 congestive heart failure, uncontrolled angina, history of myocardial infarction, unstable angina, or stroke within 6 months prior to study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication).
• Participants has uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that, in the Investigator's opinion, would put the patient at significant risk for pulmonary complications during the study.
• Participants has known active or suspected disease involvement of the central nervous system (CNS). If suspected due to clinical findings, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid.
• Participants is receiving immunosuppressive therapy, with the exception of corticosteroids (maximum dose of 10 mg prednisone or equivalent) and tacrolimus for prophylaxis of graft-versus-host disease (GVHD). If the patient has been on immunosuppressive treatment for active GVHD, the treatment(s) for active GVHD must have been discontinued at least 14 days prior to study drug and there must be no evidence of Grade .2 GVHD.
• Participants has uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness that would limit compliance with study requirements.
• Participants is pregnant or breast feeding.
• Participants has known human immunodeficiency virus (HIV).
• Participants has evidence of active or chronic Hepatitis B or Hepatitis C infection.
• Participants is oxygen-dependent.
• Participants has any medical condition that in the Investigator's opinion place the patient at an unacceptably high risk for toxicities.
• Hydroxyurea is permitted only in settings in which a patient had been receiving this agent prior to study entry; hydroxyurea may only be administered during Cycle 1. After Cycle 1, the use of hydroxyurea may be permitted in consultation with the Principal Investigator.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myelodysplastic-Myeloproliferative Diseases

Interventions

Decitabine; Injections; tagraxofusp

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Guillermo M Bravo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2021
• First Posted: September 9, 2021
• Study Start: March 4, 2022
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): January 29, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

US (1)