A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy

Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorStemline Therapeutics, Inc.

About this trial

This study will be divided into 2 parts (Part 1 and Part 2). Part 1 will evaluate 2 doses of tagraxofusp (9 and 12 micrograms/kilogram/day \[μg/kg/day\]), used in combination with venetoclax and azacitidine, to determine the dose for Part 2. This determined dose, in combination with venetoclax and azacitidine, will then be further evaluated in Part 2 in 2 cohorts (TP53 mutated and TP53 wild type). Both parts will be conducted in participants with previously untreated CD123+ AML who are ineligible for intensive chemotherapy.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Previously untreated with histological confirmation of AML by World Health Organization 2022 criteria and are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity.

Participant has any level of CD123 expression on blasts.

≥75 years of age; or

Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3.

Disqualifiers

Participant has received prior therapy for AML.

Participant is willing and able to receive standard induction therapy.

Participant has received treatment for an antecedent hematologic disease with a hypomethylating agent, venetoclax, tagraxofusp, purine analogue, cytarabine, intensive chemotherapy, SCT, chimeric antigen receptor-T therapy, or other experimental therapies.

Participant has AML with central nervous system involvement.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Tagraxofusp

    Drug

    Tagraxofusp will be administered by intravenous infusion for 3 consecutive days during each 28-day cycle.

  • Venetoclax

    Drug

    Venetoclax will be administered as an oral tablet (400 milligrams \[mg\]) daily, with ramp up in Cycle 1, and should be continued at target dose (400 mg) for the remainder of Cycle 1 and subsequent cycles of 28 days each.

  • Azacitidine

    Drug

    Azacitidine will be administered subcutaneously or by intravenous infusion (75 milligrams/square meter) over 7 days of each 28-day cycle, per institutional guidelines/physician choice.

Treatment groups

83 Participants
are divided into 4 treatment groups
Group A: Part 1 - Tagraxofusp (9 μg/kg/day)Experimental treatment 3 interventions
Group B: Part 1 - Tagraxofusp (12 μg/kg/day)Experimental treatment 3 interventions
Group C: Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild TypeExperimental treatment 3 interventions
Group D: Part 2 - Tagraxofusp (Selected Dose) and TP53 MutatedExperimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Part 1: Determination of Part 2 Selected Dose of Tagraxofusp When Administered in Combination with Venetoclax and Azacitidine

Time frame
Cycles 1-4 (up to 112 days; 28 days/cycle)
2

Part 2: Number of Participants Achieving a Best Overall Response (BOR) of Complete Remission (CR)

Time frame
Cycles 1-4 (up to 112 days; 28 days/cycle)

Secondary outcomes

1

Parts 1 and 2: Number of Participants Achieving a BOR of CR

Time frame
Cycles 1-6 (up to 168 days; 28 days/cycle)
2

Parts 1 and 2: Time to First CR

The time to first CR will be defined as the time from randomization (Cycle 1, Day 1) to the date of first documented CR.

Time frame
Cycles 1-6 (up to 168 days; 28 days/cycle)
3

Parts 1 and 2: Duration of Response

Time frame
Cycles 1-6 (up to 168 days; 28 days/cycle)
4

Parts 1 and 2: Number of Participants Achieving a BOR of CR, CR with Incomplete Hematologic Recovery (CRi), or CR with Partial Hematologic Recovery (CRh)

Time frame
Cycles 1-4 (up to 112 days; 28 days/cycle)

Other outcomes

Sponsors and contacts

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