Summary

Objectives

Eligibility

1. Participant must be at least 1 year old at the time the trial participant or legal guardian signs the informed consent form and will be assigned as follows:
2. Adult arm: aged at least 12 years old.
3. Pediatric arm: aged 1 to 17 years old. For participants of the Escalation Part only:
4. Adult and Pediatric Arms: Confirmed diagnosis of primary or secondary AML [any subtype except acute promyelocytic leukemia (APL) and juvenile myelomonocytic leukemia (JMML)] according to World Health Organization (WHO) 2022 classification. Participants with AML must meet one of the following criteria, a), b), c) or d) and are limited to those with no available (or are ineligible) therapy with known clinical benefit. a) Primary Induction Failure (PIF) AML, defined as disease refractory to one of the following, i or ii. i) An intensive induction attempt, per institution. Induction attempts include high-dose and/or standard-dose cytarabine ± an anthracyclines/anthracenedione ± an anti-metabolite, with or without growth factor or targeted therapy containing regimens. Examples include but are not limited to:
5. One cycle of high dose cytarabine (HiDAC) containing regimen
6. One cycle of liposomal cytarabine and daunorubicin
7. Two cycles of standard dose cytarabine containing regimen ii) For adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy; PIF is defined as AML refractory to one of the following less intensive regimens, 1 or 2: 1. 4 cycles of hypomethylating agents (HMA) or
8. 2 cycles HMA + venetoclax b) Early relapse (ER) AML, defined as AML in relapse with CR duration < 6 months on prior induction treatment c) Leukemia in first or higher relapse d) For participants aged 1 to 17 years old, primary induction failure is defined as disease refractory after two cycles of induction therapy.
9. Adult arm only: Confirmed diagnosis of cluster of differentiation 123 (CD123) + HR-MDS, with a Revised International Prognostic Scoring System (IPSS-R) risk category of intermediate or higher and are limited to those with no available (or are ineligible) therapy with known clinical benefit.
10. Not eligible for induction therapy and having completed =2 cycles of any of the following: hypomethylating agent (eg, 5 azacitidine or decitabine) and/or venetoclax, chemotherapy, or targeted agents.
11. Not eligible for autologous stem cell transplant (ASCT) and having completed =1 course of induction therapy.
12. Adult and Pediatric arms and escalation part only: Confirmed diagnosis of CD123+ B-ALL without extramedullary lesions that have no available (or are ineligible) therapy with known clinical benefit. For Participants in the Expansion Part Only (Adults only):
13. For participants in Cohort A: Participants meeting inclusion criteria for AML participants that have been primary refractory (PIF) to prior induction treatment or who have had ER occurring 6 months or less after an initial remission on prior induction treatment.
14. For participants in Cohort B: Participants meeting inclusion criteria for AML participants that have had late relapse (LR), occurring more than 6 months after an initial remission on prior induction treatment.
15. Body weight at least 10 kg.
16. Pediatric arm and escalation part only: Confirmed diagnosis of BPDCN according to World Health Organization (WHO) 2022 classification, who have relapsed or refractory disease with no available (or are ineligible) therapy with known clinical benefit.
17. Pediatric arm and expansion part only: For participants in Cohort C: Participants with AML who have relapsed according to inclusion criteria for AML or have recurrent disease resistant or intolerant to available therapies.

Treatment Sites in Georgia