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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05233618
• Other study ID #: HSR210434
• Status: Recruiting
• Phase: Phase 1
• Start date: July 13, 2022
• Est. completion date: October 1, 2026

Study information

• Verified date: April 2024
• Source: University of Virginia
• Contact: Danyelle Coley
• Phone: 14349825027
• Email: JCS6RZ[@]uvahealth.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: October 1, 2026
• Est. primary completion date: July 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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 × 10?/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 × 10?/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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Chronic Myelomonocytic Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• Tagraxofusp
inpatient on days 1-3 of cycles 1-4 and days 1-2 of additional cycles

Locations

Country	Name	City	State
United States	Danyelle Coley	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Karen Ballen, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of grade = 3 adverse events	Severity is based upon CTCAE v5 criteria.	Through about 30 days following last infusion of tagraxofusp
Primary	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
Primary	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	Time from HCT to relapse and death or last contact.	Duration	Participants will be followed through 2 years after date of HCT
Secondary	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