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

• Status: Not yet recruiting
• Trial end date: 2026-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Karen Ballen, MD

Criteria

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)

• Creatinine clearance > 60 ml/min (using Cockcroft-Gault equation)

• 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 > 100,000/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

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. Lack of morphologic remission at study registration

9. Requirement of supplemental oxygen

10. 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)

11. 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

12. 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

13. Known positive status for human immunodeficiency virus or active or chronic Hepatitis B or Hepatitis C

14. Receiving treatment for known or suspected fungal infection (prophylaxis is acceptable)

15. Known positive SARS-COV-2 test within 3 weeks of study entry

16. Pedal edema >= grade 2