Study of Tagraxofusp for Post-Transplant Maintenance for Patients With CD 123+ AML, MF and CMML (HSCT 002)

Phase I Study of Tagraxofusp for Post-Transplant Maintenance for Patients With CD 123+ Acute Myeloid Leukemia, Myelofibrosis and Chronic Myelomonocytic Leukemia

In this study, tagraxofusp (Tag) is given to patients with CD 123+ myelofibrosis (MF), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) after allogeneic stem cell transplant (HCT) to help prevent relapse. Patients will receive up to about 9 cycles of treatment with Tag and have a bone marrow biopsy after cycle 4 and about 1 year after HCT.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia
• Intervention / Treatment: Drug: Tagraxofusp

Detailed Description

Relapsed disease is the primary cause of treatment failure after hematopoietic cell transplant (HCT). In this study, patients are given increasing levels of tagraxofusp (Tag) to evaluate the safety of each dose. Participants will start treatment with Tag starting between 60 and 120 days following HCT. Tag will be given by IV over about 15 minutes on days 1 through 3 of cycles 1-4 of treatment (28 day cycles) and then on days 1 and 2 of subsequent cycles, for up to 9 cycles or until disease progression or if you have a bad side effect. In the first cycle, Tag will be given while participants are inpatient. In all other cycles, Tag will be given outpatient and participants will be observed for 4 hours following each infusion. After about 4 cycles of treatment and again about 1 year after HCT, participants will have a bone marrow biopsy and also take a questionnaire about their quality of life. During the study, participants will have their blood checked regularly to monitor for side effects.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Danyelle Coley; Phone Number: 14349825027; Email: JCS6RZ@uvahealth.org
• Study Contact Backup: Name: Samantha Brooks; Phone Number: 4349823365; Email: SNB3GC@uvahealth.org

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22901
      • Recruiting
      • Danyelle Coley
      • Contact: Danyelle Coley; Phone Number: 434-982-5027; Email: JCS6RZ@uvahealth.org
      • Contact: Samantha Brooks; Phone Number: 4345541718; Email: SNB3GC@uvahealth.org
      • Principal Investigator: Karen Ballen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient is ≥18 years old and ≤ 75 years old.
2. The patient has a life expectancy of >6 months.
3. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.

4. The patient has adequate baseline organ function, including cardiac, renal, and hepatic function within 28 days of start of therapy:

   • Left ventricular ejection fraction (LVEF) ≥ 50% as measured by multigated acquisition scan (MUGA) or 2-dimensional (2-D) echocardiogram (ECHO) and no clinically significant abnormalities on a 12-lead electrocardiogram (ECG)
   • Serum Creatinine ≤ 1.5 mg/dL
   • Bilirubin ≤1.5 mg/dL
   • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN)
   • Absolute neutrophil count (ANC) ≥0.5 × 10⁹/L
   • Platelets ≥ 80,000/mm^3
   • Serum albumin ≥3.2 (note that albumin infusions are not permitted in order to enable eligibility)

5. Patient meets the 2016 WHO diagnostic criteria for MF, is CD 123+, and has an IPSS/DIPSS/DIPSS-plus intermediate-1 with anemia (Hb < 10g/dl), splenomegaly (> 12 cm), leukocytosis (WBC > 25K) intermediate-2 or high-risk disease pre transplant.

   Or

   Patient has a 2016 WHO-defined diagnosis of CMML (persistent monocytosis ≥1 × 10⁹/L for at least 3 months, with other causes excluded, and monocytes ≥10% of WBC in peripheral blood, no criteria and no previous history of CML, ET, PV, and acute promyelocytic leukemia) pre transplant and is CD123+

   Or

   Patient has 2016 WHO-defined CMML-1 (2-4% blasts in peripheral blood and/or 5-9% blasts in bone marrow) and CMML-2 (5-19% blasts in peripheral blood and/or 10-19% blasts in bone marrow, and/or presence of Auer rods) pre transplant and is CD 123+

   Or

   Patient has CD 123+ AML in morphologic remission pre transplant

6. Receipt of first allogeneic stem cell transplant (related, unrelated, haploidentical or cord blood) 60-120 days prior to study registration
7. Patient is in morphologic remission post-HCT and at the time of study registration
8. Provision of signed and dated informed consent form
9. Stated willingness to comply with all study procedures and availability for the duration of the study
10. For females and males of reproductive potential: agreement to use adequate contraception for at least one month prior to screening, during study participation and for an additional one week after the end of study drug administration. Other (non-study) medications may require participants to use adequate contraception for longer.
11. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner. Other (non-study) medications may require participants to use adequate contraception for longer.
12. Agreement to adhere to Lifestyle Considerations throughout study duration

Exclusion Criteria:

1. Treatment with any disease-related therapy, including radiation therapy or investigational agent, within 14 days of study entry
2. Previous treatment with tagraxofusp or known hypersensitivity to any components of the drug product
3. Active malignancy and/or cancer history (excluding myeloproliferative disorders and concomitant myeloid malignancies as specified in the inclusion criteria) that can confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of entry) and/or ongoing active malignancy or substantial potential for recurrence must be discussed with the Sponsor before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ (including superficial bladder cancer), cervical intraepithelial neoplasia, or organ-confined prostate cancer with no evidence of progressive disease.
4. Known active or suspected disease involvement of the central nervous system (CNS)
5. Receiving > 10 mg prednisone daily for GVHD
6. Overall Grade 2 or greater acute GVHD (per Magic criteria) at time of registration
7. Pregnant or breast feeding
8. Requirement of supplemental oxygen
9. 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 or stroke within 6 months of study entry, uncontrolled hypertension or clinically significant arrhythmias not controlled by medication)
10. Uncontrolled, clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, pulmonary hypertension) that in the opinion of the Investigator would put the patient at significant risk for pulmonary complications during the study
11. Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, disseminated intravascular coagulation, or psychiatric illness/social situations that would limit compliance with study requirements
12. Known positive status for human immunodeficiency virus or active or chronic Hepatitis B or Hepatitis C
13. Receiving treatment for known or suspected fungal infection (prophylaxis is acceptable)
14. Known positive SARS-COV-2 test within 3 weeks of study entry. Exception: Tests that reflect past, resolved infection where the patient is determined to NOT be infectious, according to an infectious disease specialist, do not exclude the patient from participation.
15. Pedal edema ≥ grade 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tagraxofusp (escalating doses); IV tagraxofusp on days 1-3 of cycles 1-4 and days 1-2 of additional cycles for up to 9 cycles (some participants could receive more if considered in their best interest)	Drug: Tagraxofusp; inpatient on days 1-3 of cycles 1-4 and days 1-2 of additional cycles; Other Names: SL-701, Elzonris

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of grade ≥ 3 adverse events	Severity is based upon CTCAE v5 criteria.	Through about 30 days following last infusion of tagraxofusp
Dose limiting toxicities	Frequencies of certain, more severe, types of side effects from the study drug	During cycles 1 and 2 (each cycle is 28 days) of study treatment for each participant
Percent of planned tagraxofusp dose received	During cycles 1-4 only	Through cycle 4 (each cycle is 28 days) of study treatment for each participant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from HCT to relapse and death or last contact.	Duration	Participants will be followed through 2 years after date of HCT
Frequency and severity of acute GVHD grades II-IV and chronic GVHD	Mild, moderate or severe per Magic criteria	Participants will be followed through 2 years after date of HCT

Collaborators and Investigators

• Sponsor: Karen Ballen, MD
• Investigators: Principal Investigator: Karen Ballen, UVA

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 31, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Hematopoietic Stem Cell Transplant
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Primary Myelofibrosis; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile
• Other Study ID Numbers: HSR210434

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No