Tagraxofusp and Low-Intensity Chemotherapy for CD123-Positive Relapsed or Refractory AML

Trial Title: Tagraxofusp and Low-Intensity Chemotherapy for CD123-Positive Relapsed or Refractory AML

NCT ID: NCT06561152

Condition: Refractory Acute Myeloid Leukemia
Relapsed Acute Myeloid Leukemia

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Cytarabine
Cladribine

Conditions: Keywords:
tagraxofusp
cladribine
cytarabine

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Tagraxofusp
Description: Tagraxofusp is administered by intravenous infusion (IV) over 15 minutes for 3 consecutive days of a 28-day cycle. (days 4-6)
Arm group label: Dose Level -1 (DL-1)
Arm group label: Dose level 1 (DL1)
Arm group label: Dose level 2 (DL2)
Arm group label: Dose level 3 (DL3)

Intervention type: Drug
Intervention name: Cladribine (CLAD)
Description: Cladribine 5mg/m2 IV once daily on days 1-3 (DL1) Cladribine 5mg/m2 IV once daily on days 1-4 (DL2) Cladribine 5mg/m2 IV once daily on days 1-5 (DL3)
Arm group label: Dose Level -1 (DL-1)
Arm group label: Dose level 1 (DL1)
Arm group label: Dose level 2 (DL2)
Arm group label: Dose level 3 (DL3)

Intervention type: Drug
Intervention name: Cytarabine
Description: Cytarabine 20mg/m2 IV daily days 1-5 (DL1) Cytarabine 20mg/m2 IV daily days 1-7(DL2) cytarabine 20mg/m2 IV daily days 1-10 (DL3)
Arm group label: Dose Level -1 (DL-1)
Arm group label: Dose level 1 (DL1)
Arm group label: Dose level 2 (DL2)
Arm group label: Dose level 3 (DL3)

Summary: To determine the efficacy of the combination of tagraxofusp, cladribine, and cytarabine.

Criteria for eligibility:
Criteria:
Inclusion Criteria - Documented diagnosis of relapsed or refractory acute myeloid leukemia (AML) according to World Health Organization (WHO) 2022 criteria - Expression of CD123 by either flow cytometry or immunohistochemical staining with no minimum threshold for positivity - Must have received initial therapy with venetoclax in combination with a hypomethylating agent (either azacitidine or decitabine) with no subsequent therapy unless mutations in the IDH or FLT3 genes. If mutations in the IDH or FLT3 genes, treatment with IDH or FLT3 inhibitors after initial failure of venetoclax plus HMA is allowed, but not required. - Age ≥ 18 years of age - ECOG ≤ 2 - Albumin ≥ 3.2 g/dL at time of screening (note that albumin supplementation is not permitted to enable eligibility) - Left ventricular ejection fraction ≥ 50% - No clinically significant abnormalities on 12-lead electrocardiogram (ECG) including: complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval >250ms, or QTcF (Friderica's method) >450ms in 3 successive measurements - Stated willingness to comply with all study procedures and availability for the duration of the study - Females of reproductive potential need to either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with highly effective contraception without interruption prior to starting treatment, during the study therapy, and for 30 days after last dose of study therapy - For males of reproductive potential: agreement to use of condoms - Adequate hepatic/renal function defined as: Hepatic function: total bilirubin ≤ 1.5 x ULN (unless attributable to Gilbert's disease or leukemic involvement) AND AST or ALT ≤ 3 x ULN Renal function: creatinine clearance > 30 mL/minute, calculated by Cockcroft Gault formula - Women of childbearing potential must have a negative urine or serum pregnancy test - Ability to understand and the willingness to provide written informed consent. Exclusion Criteria: - Prior therapy apart from Venetoclax in combination with a hypomethylating agent, or Venetoclax in combination with a hypomethylating agent followed by monotherapy with IDH or FLT3 inhibitors - Patients who received systemic anti-cancer therapy <14 days prior to their first day of study drug administration. - Patients who received systemic anti-cancer therapy <14 days prior to their first day of study drug administration. Concurrent hydroxyurea will be allowed. Hydroxyurea use will be allowed only during the first cycle if needed for disease control. - Significant cardiac disease (any NYHA Class 3 or 4 CHF, uncontrolled angina, history of MI, unstable angina or stroke within 6 months prior to study entry, uncontrolled hypertension, or clinically significant arrhythmias not controlled by medication) - Any uncontrolled bacterial, fungal, viral or other infection. - Known HIV+ or active hepatitis B or C infection, defined as positive viral load for HBV or HCV or a positive surface antigen (HBsAg) test for hepatitis B. - The patient has persistent clinically significant toxicities Grade >/= 2 from previous therapies not readily controlled by supportive measures (excluding alopecia, nausea, and fatigue). - The patient has an active malignancy and/or cancer history that may confound the assessment of the study endpoints. Patients with a past cancer history (within 2 years of study entry) with substantial potential for recurrence and/or ongoing active malignancy must be discussed with study team before study entry. Patients with the following neoplastic diagnoses are eligible: non-melanoma skin cancer, carcinoma in situ, cervical intraepithelial neoplasia, organ-confined prostate cancer with no evidence of progressive disease. - The patient has 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. - The patient has known active or suspected CNS disease. If suspected, CNS disease should be ruled out with relevant imaging and/or examination of cerebrospinal fluid. - The patient is receiving immunosuppressive therapy - with the exception of low-dose prednisone (

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Stanford University

Address:
City: Palo Alto
Zip: 94304
Country: United States

Contact:
Last name: Woo In (Yustina) Cho

Phone: 650-721-2443
Email: wooin@stanford.edu

Investigator:
Last name: Gabriel Mannis
Email: Principal Investigator

Start date: October 2024

Completion date: October 2028

Lead sponsor:
Agency: Stanford University
Agency class: Other

Collaborator:
Agency: Stemline Therapeutics, Inc.
Agency class: Other

Source: Stanford University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06561152