Tagraxofusp and Low-Intensity Chemotherapy for CD123-Positive Relapsed or Refractory AML
Phase 1
Not yet recruiting
- Conditions
- Interventions
- Registration Number
- NCT06561152
- Lead Sponsor
- Stanford University
- Brief Summary
To determine the efficacy of the combination of tagraxofusp, cladribine, and cytarabine.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 20
Inclusion Criteria
Not provided
Read More
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 (</= 10 mg/day).
- Received allogenic stem cell transplant prior to the treatment.
- The patient has an 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.
- Pregnant or breast feeding
Read More
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose level 1 (DL1) Cladribine (CLAD) DL1 will consist of cladribine 5mg/m2 IV once daily on days 1-3, cytarabine 20mg/m2 IV daily days 1-5, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose level 2 (DL2) Cladribine (CLAD) DL2 will consist of cladribine 5mg/m2 IV once daily on days 1-4, cytarabine 20mg/m2 IV daily days 1-7, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose level 3 (DL3) Cladribine (CLAD) DL3 will consist of cladribine 5mg/m2 IV once daily on days 1-5, cytarabine 20mg/m2 IV daily days 1-10, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose Level -1 (DL-1) Cladribine (CLAD) DL -1 will consist of cladribine 5mg/m2 IV once daily on days 1-2, cytarabine 20mg/m2 IV daily days 1-4, and tagraxofusp 12mcg/kg IV daily days 4-6. Dose level 1 (DL1) Tagraxofusp DL1 will consist of cladribine 5mg/m2 IV once daily on days 1-3, cytarabine 20mg/m2 IV daily days 1-5, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose level 1 (DL1) Cytarabine DL1 will consist of cladribine 5mg/m2 IV once daily on days 1-3, cytarabine 20mg/m2 IV daily days 1-5, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose level 2 (DL2) Tagraxofusp DL2 will consist of cladribine 5mg/m2 IV once daily on days 1-4, cytarabine 20mg/m2 IV daily days 1-7, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose level 2 (DL2) Cytarabine DL2 will consist of cladribine 5mg/m2 IV once daily on days 1-4, cytarabine 20mg/m2 IV daily days 1-7, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose level 3 (DL3) Tagraxofusp DL3 will consist of cladribine 5mg/m2 IV once daily on days 1-5, cytarabine 20mg/m2 IV daily days 1-10, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose level 3 (DL3) Cytarabine DL3 will consist of cladribine 5mg/m2 IV once daily on days 1-5, cytarabine 20mg/m2 IV daily days 1-10, and tagraxofusp 12 mcg/kg IV daily days 4-6. If a DLT is encountered in the first 2 participants, 3 more will be enrolled at the same dose. Dose Level -1 (DL-1) Tagraxofusp DL -1 will consist of cladribine 5mg/m2 IV once daily on days 1-2, cytarabine 20mg/m2 IV daily days 1-4, and tagraxofusp 12mcg/kg IV daily days 4-6. Dose Level -1 (DL-1) Cytarabine DL -1 will consist of cladribine 5mg/m2 IV once daily on days 1-2, cytarabine 20mg/m2 IV daily days 1-4, and tagraxofusp 12mcg/kg IV daily days 4-6.
- Primary Outcome Measures
Name Time Method Recommended Phase 2 dose up 2 years Determination of the recommended Phase 2 dose based on the safety of tagraxofusp in combination with cladribine and low-dose cyatarabine, as determined by DLT evaluation.
- Secondary Outcome Measures
Name Time Method Overall response rate (ORR) up 2 years ORR will be determined by the proportion of study subjects achieving Complete Remission (CR), Complete remission with incomplete hematologic recovery (CRi), Complete remission with partial hematologic recovery (CRh), Morphological leukemia-free state (MLFS), or (Partial Response (PR), as defined by the ELN 2022 AML response criteria.
Complete response up 2 years Complete Response will be determined by the proportion of study subjects achieving CR, as defined by the ELN 2022 AML Response Criteria.
Composite complete response (CR+CRi +CRh) up 2 years Composite complete response will be determined by the proportion of study subjects achieving CR, CRi, or CRh, as defined by the ELN 2022 AML Response Criteria.
Duration of overall survival up 2 years Overall survival (OS) will be measured as the date of enrollment in the study to the date of death from any cause.
Rate of Minimal Residual Disease (MRD) negativity in responders up 2 years Rate of MRD negativity in responders, as measured by multi-parameter flow cytometry.
Incidence of drug-related adverse events up 2 years The Incidence of Drug-Related Adverse Events is a safety endpoint used to evaluate the frequency and severity of adverse events (AEs) that are attributed to the study drug All grades of adverse events determined to be treatment-related will be summarized descriptively.
Trial Locations
- Locations (1)
Stanford University
🇺🇸Palo Alto, California, United States