Using tagraxofusp to prevent relapse in patients with certain blood cancers after stem cell transplant

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

This study is testing if a new treatment called tagraxofusp can help prevent relapse in patients with certain blood cancers after they have a stem cell transplant.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 44 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: University of Virginia (other)
• Drugs / interventions: radiation, prednisone
• Locations: 2 sites (Philadelphia, Pennsylvania and 1 other locations)
• Trial ID: NCT05233618 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of tagraxofusp in patients with CD 123+ myelofibrosis, chronic myelomonocytic leukemia, and acute myeloid leukemia following allogeneic stem cell transplant. Participants will receive up to 9 cycles of treatment starting between 60 and 120 days post-transplant, with doses administered intravenously over several days. The study includes regular monitoring through blood tests and bone marrow biopsies to assess treatment response and side effects. Quality of life will also be evaluated through questionnaires at specified intervals.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with specific blood cancers who have undergone a stem cell transplant and meet certain health criteria.

Not a fit: Patients with a life expectancy of less than 6 months or those with severe organ dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of relapse in patients after stem cell transplant.

How similar studies have performed: While this approach is novel in this specific context, similar therapies targeting CD 123+ cancers have shown promise in other studies.

Eligibility 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)
   * 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

   Or

   Patient has Intermediate or high risk MDS by IPSS-R or moderate or high risk by IPSS-M pre transplant and has had no morphologic progression of disease post-transplant.

   Receipt of first allogeneic stem cell transplant (related, unrelated, haploidentical or cord blood) 60-120 days prior to study registration
6. Patient is in morphologic remission according to bone marrow biopsy completed within 30 days prior to planned start of study treatment
7. Provision of signed and dated informed consent form
8. Stated willingness to comply with all study procedures and availability for the duration of the study
9. 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.
10. 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.
11. 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

Where this trial is running

Philadelphia, Pennsylvania and 1 other locations

• Thomas Jefferson University — Philadelphia, Pennsylvania, United States (RECRUITING)
• University of Virginia — Charlottesville, Virginia, United States (RECRUITING)

Study contacts

• Principal investigator: Karen Ballen — UVA
• Study coordinator: Samantha Brooks

Conditions: Myelofibrosis, Chronic Myelomonocytic Leukemia, Acute Myeloid Leukemia, Hematopoietic Stem Cell Transplant