Study of Cell Therapies for Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome

Sponsor

Arcellx, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05457010

Collaborator

(none)

Enrollment

Arm

37.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Master protocol designed to investigate safety, tolerability, PK, PD, and preliminary activity for targeted investigational cell therapies

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes	Biological: SPRX002 Biological: ARC-T	Phase 1

Detailed Description

Proof-of-concept studies for the sponsor, Arcellx, Inc., in relapsed or refractory acute myeloid leukemia(AML) and high-risk myelodysplastic syndromes (MDS) and includes long-term safety follow-up. The overall framework for the studies is included in this Master protocol and will apply to the unique study ARMS included now and in the future.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Master Protocol for the Phase 1 Study of Cell Therapies for the Treatment of Patients With Relapsed or Refractory Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome, Including Long-term Safety Follow-up

Anticipated Study Start Date :

Sep 30, 2022

Anticipated Primary Completion Date :

Sep 30, 2025

Anticipated Study Completion Date :

Nov 17, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CD123-Specific Adapter (SPRX002) and Universal CAR-Modified T Cell (ARC-T Cells) Arm 1: Phase 1 Study of monovalent CD123-Specific Adapter (SPRX002) and Universal CAR-Modified T cell (ARC-T Cells) for the Treatment of Patients with Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes	Biological: SPRX002 SPRX002 is a soluble protein with a "TAG" region to which ARC-T cells bind and a binding region targeting CD123. Other Names: in combination with ARC-T called ACLX002 Biological: ARC-T ARC-T cells is a genetically modified autologous T-cell product. The T cell has a binding domain chimeric antigen receptor (CAR), which specifically binds to the "TAG" protein of the soluble protein antigen-receptor x-linker (sparX; specifically, SPRX002). When ARC-T cells bind to a "TAG" and the SPRX protein is bound to its target (in this case CD123), ARC-T cells are capable of activation, expansion, and killing (based on preclinical experiments). Other Names: in combination with SPRX002 called ACLX002

Arm

Intervention/Treatment

Experimental: CD123-Specific Adapter (SPRX002) and Universal CAR-Modified T Cell (ARC-T Cells)

Arm 1: Phase 1 Study of monovalent CD123-Specific Adapter (SPRX002) and Universal CAR-Modified T cell (ARC-T Cells) for the Treatment of Patients with Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

Biological: SPRX002

SPRX002 is a soluble protein with a "TAG" region to which ARC-T cells bind and a binding region targeting CD123.

Other Names:

in combination with ARC-T called ACLX002

Biological: ARC-T

ARC-T cells is a genetically modified autologous T-cell product. The T cell has a binding domain chimeric antigen receptor (CAR), which specifically binds to the "TAG" protein of the soluble protein antigen-receptor x-linker (sparX; specifically, SPRX002). When ARC-T cells bind to a "TAG" and the SPRX protein is bound to its target (in this case CD123), ARC-T cells are capable of activation, expansion, and killing (based on preclinical experiments).

Other Names:

in combination with SPRX002 called ACLX002

Outcome Measures

Primary Outcome Measures

Adverse Events and Dose-Limiting Toxicities [24 months]
Review the number of adverse events and dose-limiting toxicities for all subjects to determine a recommended phase 2 dose

Secondary Outcome Measures

Anti-tumor activity [24 months]
Measure serial blood and bone marrow results to determine response by International Working Group (IWG) Response Criteria to review overall response rate, complete remission rate, and negative minimum residual disease (MRD)
Pharmacokinetics (PK) profile [24 months]
Collect blood samples to determine the drug concentration of ARC-T and SPRX002 in the subject

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

18 years or older
For AML subjects: WHO-confirmed AML (2016 criteria) with no standard treatment options
Relapsed or refractory disease after 1 or 2 lines of therapy
relapsed: bone marrow blasts ≥ 5% following achievement of CR/CRi/MLFS
refractory: failure to achieve CR/CRi/MLFS with evidence of persistence leukemia by blood or bone marrow after: i. at least 2 cycles of 7+3 based therapy ii. at least 1 cycle of high or intermediate dose cytarabine containing induction regimen iii. at least 2 cycles of VEN-based lower intensity therapy iv. at least 4 cycles of HMA-based therapy with ventoclax
For MDS subjects: diagnosis of MDS and ≥ 10% bone marrow blasts with indication of high risk disease defined as resistant or refractory disease to at least one course of therapy including hypomethelating agents with or without ventoclax
Must have an identified potential donor and transplant strategy/plan prior to initiation of lymphodepletion regimen.

Exclusion Criteria:

Patients with APL (acute promyelocytic leukemia)
Patients with active CNS involvement
hyperleukocytosis or rapidly progressing disease
previous treatment with an investigational gene or chimeric antigen receptor therapy
previous treatment with an anti-CD123 directed therapy