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

NCT05457010 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: ARC-201
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

Master Protocol: The main goal of this master clinical trial study is to assesses the safety, tolerability, pharmacokinetic (PK), Pharmacodynamic (PD) in participants with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). The goal of the Arm 1 study is to assess the safety, tolerability, PK, and PD of the study drugs, Antigen Receptor Complex T (ARC-T) cells and CD123-specific soluble protein antigen-receptor X-linker (SPRX002), in participants with relapsed or refractory AML or MDS. The primary objective of this study is to assess the safety profile (including any dose-limiting toxicity (DLT)), to determine recommended Phase 2 dose (RP2D) of the investigational agents when infused in participants with relapsed and refractory AML or MDS.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Keywords

Arcellx; ARC-T cells; SparX; SPRX002; ACLX-002

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)

  First dose date up to 24 months, plus 90 days following last SPRX002 dose

• Percentage of Participants Experiencing Dose-Limiting Toxicities (DLT)

  Up to 28 days following SPRX002 + ARC-T infusion

• Recommended Phase 2 Dose (RP2D)

  RP2D will be determined based on the totality of data, including the maximum tolerated dose (MTD); if applicable, and other endpoints such as observed efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and other safety endpoints (adverse events (AEs), laboratory assessment, vital signs, and physical examinations).

  Up to 24 months

Secondary Outcomes (2)

• Anti-Tumor Activity

  Up to 24 months

• Pharmacokinetics (PK)

  Up to 24 months

Study Arms (1)

ARM 1: SPRX002 + ARC-T Cells

EXPERIMENTAL

Participants with relapsed or refractory AML or high-risk MDS will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of ARC-T cells and multiple doses of SPRX002.

Biological: SPRX002; Biological: ARC-T Cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

SPRX002 BIOLOGICAL

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

ARM 1: SPRX002 + ARC-T Cells

ARC-T Cells BIOLOGICAL

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). Administered intravenously.

ARM 1: SPRX002 + ARC-T Cells

Cyclophosphamide DRUG

Administered intravenously

ARM 1: SPRX002 + ARC-T Cells

Fludarabine DRUG

Administered intravenously

ARM 1: SPRX002 + ARC-T Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• For AML Individuals: WHO-confirmed AML, other than APL, with no standard treatment options available (WHO AML Criteria 2016)
• a. Relapsed or refractory disease after at least 1 line of therapy, as defined by the following: i. Relapsed: Bone marrow blasts ≥5% following achievement of CR/Cri/MLFS
• ii. Refractory: Failure to achieve CR/Cri/MLFS with evidence of persistent leukemia by blood and/or bone marrow examination after any of the following:
• Failure on at least 1 cycle of an anthracycline-based induction therapy
• At least 1 cycle of high or intermediate dose cytarabine containing induction regimen
• At least 2 cycles of VEN-based lower intensity therapy, e.g., with HMA, or LDAC or cladribine+LDAC
• At least 4 cycles of HMA-based therapy without venetoclax
• For MDS Individuals: A diagnosis of MDS and ≥10% bone marrow blasts with indication of high-risk disease defined as those having resistant or refractory disease to at least one course of therapy including hypomethylating agents (e.g., decitabine or 5-azacitidine) given at conventional dose, schedule, and duration (e.g., cycle every 28 days and for at least 4 cycles) with or without venetoclax or other agents. Failure is defined as failure to attain a response, or relapse after prior response to HMA therapy per the modified IWG criteria.
• \. Patients relapsing after allogeneic hematopoietic stem cell transplant (HSCT) \>3 months prior are eligible if they have recovered from all transplant-related toxicities and are off all immunosuppression for at least 6 weeks.
• \. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• \. Adequate organ function, including renal and hepatic function based on last clinical assessment performed within the screening period
• Creatinine clearance ≥50 ml/min (Cockcroft-Gault or 24-hour urine collection in cases in which Cockroft-Gault is unreliable or if preferred by physician) and not on dialysis
• Alanine aminotransferase \<3 x upper limit of normal (ULN)
• Aspartate aminotransferase \<3 x the upper limit of normal (ULN)

You may not qualify if:

• Patients with acute promyelocytic leukemia (APL) or EMD-only disease
• Patients with active CNS involvement. Individuals may be cleared of CNS involvement if there has been no evidence of CNS involvement for at least 3 months prior to enrollment. For instance, CSF samples showing no evidence of blasts by CSF cytology, no clinical signs or symptoms, or no radiological findings concerning for CNS involvement.
• Hyperleukocytosis (≥25,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy. (Note: Individuals may be receiving or may receive hydroxyurea to maintain or control hyperleukocytosis)
• Previous treatment with an investigational gene or chimeric antigen receptor therapy (Note: May be permitted after discussion with Medical Monitor)
• Previous treatment with a CD123 directed therapy (T-cell engager or ADC)
• Use of any anti-AML/MDS directed chemotherapy or targeted therapy (except hydroxyurea therapy) or immunosuppressive agents (physiologic doses are allowed), within 14 days or 5 half-lives (whichever is shorter) prior to the date of leukapheresis and use of any anti-AML/MDS directed monoclonal antibody within 28 days prior to date of leukapheresis
• Known infection with Human Immunodeficiency Virus or Human T-Cell leukemia/lymphoma virus type 1 (HTLV-1)
• A known hypersensitivity or severe allergy to study drug components including dimethyl sulphoxide (DMSO) and human serum albumin
• Contraindication to cyclophosphamide or fludarabine
• Individual has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate treatment (Note: Isolated fever may not constitute active infection in and of itself, (e.g., related to disease)
• Severe uncontrolled intercurrent illness including:
• Cardiovascular disease
• Symptomatic congestive heart failure
• Unstable angina, arrythmia, or myocardial infarction (MI) within 6 months prior to screening
• Significant pulmonary dysfunction

Sponsors & Collaborators

• Arcellx, Inc.: collaborator
• Kite, A Gilead Company: lead

Study Sites (5)

City of Hope

Duarte, California, 91010, United States

Location

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Montefiore Einstein Cancer Center

New Rochelle, New York, 10801, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Kite Study Director, MD

  Kite, A Gilead Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2022
• First Posted: July 13, 2022
• Study Start: November 28, 2022
• Primary Completion: October 1, 2026
• Study Completion: October 1, 2026
• Last Updated: October 2, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)