Tagraxofusp and Low-Intensity Chemotherapy for CD123-Positive Relapsed or Refractory AML
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorStanford University
About this trial
To determine the efficacy of the combination of tagraxofusp, cladribine, and cytarabine.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Age ≥ 18 years of age
Disqualifiers
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)
Trial design
Design model
Sequential
Treatments tested in this trial
Tagraxofusp
DrugTagraxofusp is administered by intravenous infusion (IV) over 15 minutes for 3 consecutive days of a 28-day cycle. (days 4-6)
Cladribine (CLAD)
DrugCladribine 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)
Cytarabine
DrugCytarabine 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)
Treatment groups
20 Participants
are divided into 4 treatment groupsGroup A: Dose level 1 (DL1)Experimental treatment 3 interventions
Group B: Dose level 2 (DL2)Experimental treatment 3 interventions
Group C: Dose level 3 (DL3)Experimental treatment 3 interventions
Group D: Dose Level -1 (DL-1)Experimental treatment 3 interventions
Trial outcomes
Primary outcomes
1
Recommended Phase 2 dose
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.
Time frame
up 2 yearsSecondary outcomes
1
Overall response rate (ORR)
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.
Time frame
up 2 years2
Complete response
Complete Response will be determined by the proportion of study subjects achieving CR, as defined by the ELN 2022 AML Response Criteria.
Time frame
up 2 years3
Composite complete response (CR+CRi +CRh)
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.
Time frame
up 2 years4
Rate of Minimal Residual Disease (MRD) negativity in responders
Rate of MRD negativity in responders, as measured by multi-parameter flow cytometry.
Time frame
up 2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Stanford University
Lead sponsor
Stemline Therapeutics, Inc.
Collaborator
Source ClinicalTrials.gov