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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Intervention / Treatment: Biological: SPRX002; Biological: ARC-T Cells; Drug: Cyclophosphamide; Drug: Fludarabine

Detailed Description

The study will have the following sequential phases: screening, enrollment, pretreatment with lymphodepletion (LD) chemotherapy, treatment with SPRX002 and ARCT cells, treatment extension with SPRX002, follow up, and long-term safety follow-up.

Following infusion of SPRX002 and a single infusion of ARC T (Day 0) and followed by regular administration of SPRX002 at the assigned dose level, both safety and efficacy data will be assessed. Dose limiting toxicities (DLTs) will be assessed through Day 28 and safety data will be collected throughout the study. Long-term safety data will be collected for up to 15 years per health authority guidelines. Efficacy will be assessed monthly for the first 6 months, then quarterly up to 2 years, or upon participants relapse.

ARC-T cells are a genetically modified autologous T-cell product. The T cell has been transduced using a third-generation lentiviral vector encoding a binding domain (referred to as AF101) chimeric antigen receptor (CAR), followed by CD8 spacer and transmembrane region that is fused to the intracellular signaling domains 4-1BB and CD3ζ. AF101 specifically binds to the "TAG" protein (referred to as Q26) of the soluble protein antigen-receptor x-linker (sparX; specifically, SPRX002).

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New York
    • New Rochelle, New York, United States, 10801
      • Montefiore Einstein Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. 18 years or older

2. 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:

1. Failure on at least 1 cycle of an anthracycline-based induction therapy
2. At least 1 cycle of high or intermediate dose cytarabine containing induction regimen
3. At least 2 cycles of VEN-based lower intensity therapy, e.g., with HMA, or LDAC or cladribine+LDAC
4. At least 4 cycles of HMA-based therapy without venetoclax

3.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.

4. 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.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

6. Adequate organ function, including renal and hepatic function based on last clinical assessment performed within the screening period

1. 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

2. Alanine aminotransferase <3 x upper limit of normal (ULN)

3. Aspartate aminotransferase <3 x the upper limit of normal (ULN)

4. Total bilirubin <2 x upper limit of normal (ULN) (except for patients with known or suspected history of Gilbert's Syndrome where up to 3x ULN is allowed)

5. Left Ventricular Ejection Fraction (LVEF) ≥45% by echocardiography (ECHO) or multi-gated acquisition (MUGA) scan

6. Pulse oxygenation ≥92% on room air

7. Prothrombin time test (PTT), prothrombin time (PT)/international normalized ratio (INR) <1.5 x ULN, unless on a stable dose of anti-coagulant for thromboembolic event (patients with any history of thromboembolic stroke; or history or Grade 2 (G2) or greater hemorrhage within 60 days are excluded)

   7. Resolution of adverse events (AEs) from any prior systemic anticancer therapy, radiotherapy, or surgery to Grade 1 or baseline (except G2 alopecia and G2 sensory neuropathy)

   8. Prior allogeneic stem cell transplant is allowed, provided the individual has recovered from all AEs, there is no ongoing graft-versus-host-disease (GvHD) and individual is not on taking any immunosuppressive medications to prevent GvHD

   9. Male and females of childbearing potential must agree to use highly effective methods of birth control through 6 months after the dose of study treatment.

   10. Patients must have an identified potential donor and transplant strategy/plan prior to initiation of the lymphodepletion regimen to ensure availability of hematopoeitic stem cells (HSCs) for potential urgent allogeneic HSC transplant (HSCT) if needed for persistent bone marrow aplasia without evidence of residual leukemia. Transplant decision making would be a discussion between individual and investigator due to potential for treatment-related mortality and is not required

   11. Willing to comply with and able to tolerate study procedures, including Long-Term Safety Follow-up lasting up to 15 years

   12. Life expectancy > 3 months

   13. Individual's apheresis product from non-mobilized cells is received and accepted for cell processing by manufacturing site. NOTE: apheresis will be accepted only after all other eligibility criteria have been met

Key Exclusion Criteria:

1. Patients with acute promyelocytic leukemia (APL) or EMD-only disease

2. 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.

3. 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)

4. Previous treatment with an investigational gene or chimeric antigen receptor therapy (Note: May be permitted after discussion with Medical Monitor)

5. Previous treatment with a CD123 directed therapy (T-cell engager or ADC)

6. 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

7. Known infection with Human Immunodeficiency Virus or Human T-Cell leukemia/lymphoma virus type 1 (HTLV-1)

8. A known hypersensitivity or severe allergy to study drug components including dimethyl sulphoxide (DMSO) and human serum albumin

9. Contraindication to cyclophosphamide or fludarabine

10. 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)

11. Severe uncontrolled intercurrent illness including:

    1. Cardiovascular disease
    2. Symptomatic congestive heart failure
    3. Unstable angina, arrythmia, or myocardial infarction (MI) within 6 months prior to screening
    4. Significant pulmonary dysfunction
    5. Uncontrolled thromboembolic events or recent severe hemorrhage
    6. Any history of pulmonary embolism (PE) ever or deep vein thrombosis (DVT) within 3 months of screening. Therapeutic dosing of anticoagulants (e.g., warfarin, low molecular weight heparin, Factor Xa inhibitors) is allowed for history of DVT if greater than 3 months from time of screening) Note: Central line thrombosis not requiring anticoagulation will not be excluded and will not require a 3-month screening window
    7. Autoimmune disease

12. Seropositive for and with evidence of active hepatitis B or C infection at time of Screening

    1. Individuals with a history of hepatitis B but have received antiviral therapy and have non-detectable viral DNA for 6 months are eligible
    2. Individuals seropositive because of hepatitis B virus vaccine with no signs or active infection are eligible
    3. Individuals who had hepatitis C but have received antiviral therapy and show no detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible

13. Any sign of active CNS pathology within 6 months of screening including history of epilepsy, seizure requiring anti-seizure medications, paresis, aphasia, stroke, severe brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain syndrome or psychosis. Subarachnoid hemorrhage or central nervous system (CNS) bleed within 3 months of screening

14. Individual has active malignant tumors other than AML/MDS that requires active antineoplastic or radiation therapy at the time of screening. Maintenance therapy or hormonal therapy for well-controlled malignancy is allowed

15. Females who are pregnant or breastfeeding

16. Individuals with any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the individual from participating in study (or full access to medical records) as written including follow up, the interpretation of data or place the individual at unacceptable risk are excluded

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ARM 1: SPRX002 + ARC-T Cells; 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; SPRX002 is a soluble protein with a "TAG" region to which ARC-T cells bind and a binding region targeting CD123. Administered intravenously.; Biological: ARC-T Cells; 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.; Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-Tumor Activity	Serial blood and bone marrow sampling to determine response to treatment by modified International Working Group (IWG) Response Criteria in AML and MDS, or other appropriate response criteria for the malignancy under study, such as overall response rate, composite complete remission rate, and rate of negative minimum residual disease (MRD)	Up to 24 months
Pharmacokinetics (PK)	Quantification of ARC-T cells and SPRX002 using vector copy number (VCN) on peripheral blood mononuclear cells	Up to 24 months

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Collaborators: Arcellx, Inc.
• Investigators: Study Director: Kite Study Director, MD, Kite, A Gilead Company

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2022
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: July 8, 2022
• First Submitted That Met QC Criteria: July 12, 2022
• First Posted (Actual): July 13, 2022

Study Record Updates

• Last Update Posted (Actual): October 2, 2026
• Last Update Submitted That Met QC Criteria: September 29, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Arcellx; ARC-T cells; SparX; SPRX002; ACLX-002
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: ARC-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No