Cell Therapies for Acute Myeloid Leukemia

Recruiting at 5 trial locations

Overseen By Clinical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Arcellx, Inc.

Must not be taking: Anti-AML/MDS, Immunosuppressants

Disqualifiers: APL, CNS involvement, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

24 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not use any anti-AML/MDS directed chemotherapy or targeted therapy (except hydroxyurea) within 14 days or 5 half-lives before leukapheresis, and no monoclonal antibodies within 28 days before leukapheresis.

What data supports the effectiveness of the treatment ARC-T Cells for Acute Myeloid Leukemia?

Research indicates that CD123-targeted therapies, like ARC-T Cells, show promise in treating acute myeloid leukemia (AML) due to their ability to target specific antigens on leukemia cells. However, challenges remain due to the overlap of these antigens with normal cells, which can lead to side effects. ^{1 2 3 4 5}

Is the cell therapy for acute myeloid leukemia generally safe in humans?

Research on similar cell therapies for acute myeloid leukemia shows mixed safety results. Some studies indicate that certain therapies can target leukemia cells without harming normal cells, while others suggest potential risks of damaging normal blood-forming cells, which could lead to serious side effects. ^{1 4 6 7 8}

How is the ARC-T Cells, SPRX002 treatment different from other treatments for acute myeloid leukemia?

The ARC-T Cells, SPRX002 treatment is unique because it uses engineered T cells that specifically target the CD123 antigen on leukemia cells, potentially reducing the risk of attacking normal cells. This approach aims to improve the precision and effectiveness of treatment compared to traditional therapies. ^{1 8 9 10 11}

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and preliminary activity of ARC-T cells and SPRX002 in participants with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS)

Research Team

Tim Welliver, MD, PhD

Principal Investigator

Arcellx, Inc.

Eligibility Criteria

Adults with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), who have tried certain treatments without success, can join. They must be in good general health with proper organ function and not pregnant. People are excluded if they've had recent heart issues, other active cancers needing treatment, severe infections, autoimmune diseases, or a history of certain blood clots.

Inclusion Criteria

I have been diagnosed with a high-risk form of MDS with more than 10% bone marrow blasts.

I am fully active or can carry out light work.

My kidney and liver are working well according to my last tests.

Exclusion Criteria

My cancer has spread to my brain.

I have been treated with experimental gene or CAR-T therapy before.

I have been treated with targeted therapy for my cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Enrollment

Participants are enrolled into the study after meeting eligibility criteria

1 week

Pretreatment with Lymphodepletion Chemotherapy

Participants receive lymphodepletion chemotherapy prior to cell therapy

1 week

Treatment

Participants receive a single infusion of SPRX002 and ARC-T cells followed by regular administration of SPRX002

4 weeks

Weekly visits for monitoring

Treatment Extension

Continued administration of SPRX002 to assess long-term efficacy and safety

6 months

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Monthly for 6 months, then quarterly

Long-term Safety Follow-up

Long-term safety data collection for up to 15 years as per health authority guidelines

15 years

Treatment Details

Interventions

• ARC-T Cells
• SPRX002

Trial Overview The trial is testing ARC-T cells and SPRX002 to see if they're safe and effective for patients whose AML or MDS hasn't responded to previous treatments. It's an early-phase study which means it's one of the first times these therapies are being tested in humans.

Participant Groups

Group I: CD123-Specific Adapter (SPRX002) and Universal CAR-Modified T Cell (ARC-T Cells) Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Arcellx, Inc.

Lead Sponsor

Trials

5

Recruited

650+

Findings from Research

A novel method was developed to generate large numbers of reactive T-cell lines specifically targeting acute myeloid leukemia (AML), with an estimated frequency of 6 AML-reactive T cells per million peripheral blood mononuclear cells from patients.

These T-cell lines demonstrated the ability to specifically kill autologous AML cells and induce apoptosis, particularly through CD4(+) T cells, suggesting their potential for effective adoptive immunotherapy in AML treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of T-cell lines to autologous acute myeloid leukemia cells by competitive limiting dilution culture of acute myeloid leukemia mononuclear cells. Zhong, RK., Lane, TA., Ball, ED.[2008]

B7-H3 is identified as a promising target for CAR T-cell therapy in acute myeloid leukemia (AML), as it is overexpressed on leukemic cells but not significantly on normal bone marrow progenitors, potentially reducing the risk of harming healthy cells.

B7-H3-specific CAR T-cells (B7-H3.CAR-T) demonstrated effective cytotoxicity against AML in both in vitro and patient-derived xenograft models, while showing a favorable safety profile with minimal hematopoietic toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of B7-H3-specific Chimeric Antigen Receptor T Cells for the Treatment of Acute Myeloid Leukemia. Lichtman, EI., Du, H., Shou, P., et al.[2022]

CAR T-cell therapy shows promise in improving outcomes for patients with acute myeloid leukemia (AML), a condition with historically poor prognosis.

A significant challenge for the effectiveness of CAR T-cell therapy in AML is the identification of specific target antigens on leukemia cells, as well as the risk of immune escape due to changes in these antigens and a suppressive tumor environment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current challenges for CAR T-cell therapy of acute myeloid leukemia. Sauer, T., Rooney, CM.[2020]

CD123 is confirmed as a valid target for treating acute myeloid leukemia (AML), with both 41BB-based and CD28-based CAR T-cell therapies showing strong effectiveness in eliminating AML cells in laboratory and animal models.

However, these CAR T-cell therapies also destroy normal blood stem cells, which raises safety concerns and suggests they should primarily be used as a temporary solution before a stem cell transplant in patients with refractory or relapsed AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo. Baroni, ML., Sanchez Martinez, D., Gutierrez Aguera, F., et al.[2021]

Pediatric patients with acute myeloid leukemia (AML) have poor outcomes, indicating a critical need for improved targeted therapies, particularly those similar to successful CD19-directed therapies used in acute lymphocytic leukemia (ALL).

Promising targets for AML therapies include CD123 and CD33, with ongoing research into T cell engaging bispecific antibodies and CAR T cells, which are being explored in upcoming clinical trials to enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harnessing T Cells to Target Pediatric Acute Myeloid Leukemia: CARs, BiTEs, and Beyond. Epperly, R., Gottschalk, S., Velasquez, MP.[2020]

A new modular T cell therapy platform has been developed that targets acute myeloid leukemia (AML) by using synthetic agonistic receptor (SAR) T cells combined with AML-specific antibody fragments, allowing for selective targeting of cancer cells.

This approach demonstrated effective killing of AML cells in laboratory models and showed durable responses in xenograft models, suggesting it could be a promising treatment option for AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A modular and controllable T cell therapy platform for acute myeloid leukemia. Benmebarek, MR., Cadilha, BL., Herrmann, M., et al.[2023]

The study identifies LILRB4 as a promising tumor-associated antigen specifically expressed on monocytic acute myeloid leukemia (AML) cells, allowing for targeted therapy without affecting normal blood stem cells.

The novel anti-LILRB4 CAR-T cells demonstrated effective targeting and destruction of LILRB4+ AML cells in laboratory tests, while showing no toxicity to normal hematopoietic progenitors, suggesting a safer treatment option for patients with monocytic AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Anti-LILRB4 CAR-T Cell for the Treatment of Monocytic AML. John, S., Chen, H., Deng, M., et al.[2020]

UCART123, a gene-edited CAR T cell therapy targeting the CD123 antigen, shows promise in effectively eliminating leukemia stem cells (LSCs) in acute myeloid leukemia (AML), leading to improved overall survival in mouse models.

This therapy is designed to minimize the risk of graft-versus-host disease and allows for controlled elimination of the CAR T cells using Rituximab, making it a potentially safe and effective off-the-shelf treatment option for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic TCRαβ deficient CAR T-cells targeting CD123 in acute myeloid leukemia. Sugita, M., Galetto, R., Zong, H., et al.[2022]

CD123 chimeric antigen receptor (CAR) redirected T cells have shown strong antileukemic activity, indicating a promising new approach for treating acute myeloid leukemia.

The development of CD123 CARs provides insights into enhancing immunotherapy strategies, highlighting the need for novel treatments in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia therapeutics: CARs in the driver's seat. Mardiros, A., Brown, CE., Budde, LE., et al.[2021]

CD93 has been identified as a promising target antigen for chimeric antigen receptor T-cell therapy in treating acute myeloid leukemia (AML).

The study also presents a strategy to reduce the risk of 'on-target/off-cancer toxicity,' which is a significant concern in targeted cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Employing Synthetic T-cell Biology to Target AML without On-Target/Off-Cancer Toxicity. Velasquez, MP., Gottschalk, S.[2023]

CD123 is identified as a promising target for CAR T-cell therapy in acute myeloid leukemia (AML), as its expression increases over time in tumor cells, making it a viable option for treatment.

While CART123 T cells effectively eliminate AML cells in mice, they also destroy normal blood cell production, highlighting the need for careful management and potential rescue strategies during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Gill, S., Tasian, SK., Ruella, M., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Generation of T-cell lines to autologous acute myeloid leukemia cells by competitive limiting dilution culture of acute myeloid leukemia mononuclear cells. [2008]

2. United States pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of B7-H3-specific Chimeric Antigen Receptor T Cells for the Treatment of Acute Myeloid Leukemia. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Current challenges for CAR T-cell therapy of acute myeloid leukemia. [2020]

4. England pubmed.ncbi.nlm.nih.gov

41BB-based and CD28-based CD123-redirected T-cells ablate human normal hematopoiesis in vivo. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Harnessing T Cells to Target Pediatric Acute Myeloid Leukemia: CARs, BiTEs, and Beyond. [2020]

6. England pubmed.ncbi.nlm.nih.gov

A modular and controllable T cell therapy platform for acute myeloid leukemia. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

A Novel Anti-LILRB4 CAR-T Cell for the Treatment of Monocytic AML. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Allogeneic TCRαβ deficient CAR T-cells targeting CD123 in acute myeloid leukemia. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Acute myeloid leukemia therapeutics: CARs in the driver's seat. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Employing Synthetic T-cell Biology to Target AML without On-Target/Off-Cancer Toxicity. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. [2021]