ARD103 CAR-T Therapy for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Recruiting at 1 trial location

Overseen By ARCE Therapeutics, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ARCE Therapeutics, Inc.

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: Acute promyelocytic leukemia, CNS disorder, Autoimmune disease, Hepatitis B/C, others

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

Compensation: Varies

Number of Visits: Unknown

49 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop any previous chemotherapy, biologic/targeted therapy, or immunological agents directed to the disease at least 14 days before screening and throughout the study.

What data supports the effectiveness of the ARD103 CAR-T treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome?

Research shows that CAR T-cell therapies, like those targeting CD33 and CD123, have demonstrated strong anti-leukemia effects in preclinical studies, effectively killing leukemia cells and delaying disease progression in animal models. These findings suggest that similar CAR-T treatments could be effective for acute myeloid leukemia. ^{1 2 3 4 5}

What safety data exists for ARD103 CAR-T Therapy?

In a study testing a similar type of therapy called CAR NK-92 cells for acute myeloid leukemia, no significant adverse effects were observed at doses up to 5 billion cells per patient, suggesting a favorable safety profile. ^{1 2 6 7 8}

How is the ARD103 CAR-T treatment different from other treatments for acute myeloid leukemia?

ARD103 CAR-T therapy is unique because it uses engineered T-cells to target specific antigens, CD123 and CD33, on leukemia cells, potentially reducing the risk of relapse by addressing both bulk disease and leukemic stem cells. This dual-target approach aims to overcome challenges like immune escape and antigen down-regulation that limit the effectiveness of other treatments. ^{1 4 5 8 9}

What is the purpose of this trial?

This is a phase I/2, interventional, open-label, multicenter study to assess the safety and efficacy of ARD103 in patients with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome.

Eligibility Criteria

This trial is for adults with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with ≥5% bone marrow blasts. Participants must be in good physical condition (ECOG status of 0 or 1), have a certain level of lymphocytes, liver enzymes within normal limits, adequate kidney function, and not be pregnant. They must also agree to use contraception.

Inclusion Criteria

My lymphocyte count is above 100/mm3.

I agree to use effective birth control.

My kidneys work well enough, with a creatinine clearance rate of at least 45 mL/min.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Phase 1 involves testing three escalating dose levels using the 3 + 3 design to identify the MTD and RP2D

28 days

Dose Expansion

Phase 2 involves two stages: Stage I enrolls participants treated at RP2D from Phase 1, and Stage II continues enrollment for preliminary assessment of efficacy and safety

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

Up to 15 years

Treatment Details

Interventions

• ARD103

Trial Overview The study is testing ARD103 CAR-T therapy combined with chemotherapy drugs Cyclophosphamide and Fludarabine. It's an early-stage trial to see if this treatment is safe and works against AML/MDS that has come back or hasn't responded to other treatments.

Participant Groups

Group I: phase 1 (Dose Escalation) and phase 2 (Dose Expansion) Experimental Treatment 3 Interventions

In Phase 1, three escalating dose levels will be tested using the 3 + 3 design. The MTD and RP2D will be identified. The Phase 2 will be conducted in 2 stages. In Stage I, evaluable participants from Phase 1 treated at RP2D will be enrolled. And the enrollment will continue into Stage II (additional evaluable participants) at the maximum RP2D participants for preliminary overall assessment of efficacy and safety.

Who Is Running the Clinical Trial?

ARCE Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

50+

Findings from Research

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]

CAR T-cell therapy has the potential to improve outcomes for patients with acute myeloid leukemia (AML) by specifically targeting leukemia cells, but there are significant challenges to its effectiveness and safety.

Strategies being explored to enhance CAR T-cell therapy in AML include targeting specific leukemia antigens to reduce side effects, using checkpoint inhibitors to counteract immune suppression caused by leukemia, and developing allogenic CAR T cells to make the treatment more accessible to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospect of CAR T-cell therapy in acute myeloid leukemia. Badar, T., Manna, A., Gadd, ME., et al.[2022]

A novel second-generation chimeric antigen receptor (CAR) targeting CD33 has been developed, showing effectiveness in redirecting T cells to kill acute myeloid leukemia (AML) cells, which express CD33 in about 90% of cases.

In pre-clinical studies, this CAR therapy demonstrated significant anti-leukemia effects both in vitro and in vivo, effectively preventing leukemia development and delaying disease progression in mice, supporting its potential as a clinical treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. O'Hear, C., Heiber, JF., Schubert, I., 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 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]

In a study testing CD33-CAR NK cells in patients with relapsed and refractory acute myeloid leukemia (AML), no significant adverse effects were observed at doses up to 5 billion cells per patient, suggesting a favorable safety profile.

CAR NK-92 cells can be produced at a lower cost than CAR T cells, indicating that with further optimization, they could become a more accessible treatment option for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. Tang, X., Yang, L., Li, Z., et al.[2021]

FLT3L CAR-T cells specifically target and kill FLT3+ leukemia cells, including those with the FLT3-ITD mutation, showing strong potential for treating acute myeloid leukemia (AML).

In mouse models, FLT3L CAR-T therapy significantly prolonged survival without harming normal hematopoietic stem cells, indicating a promising safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells. Wang, Y., Xu, Y., Li, S., et al.[2019]

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]

The compound CAR (cCAR) T-cell therapy, which targets both CD123 and CD33 antigens in acute myeloid leukemia (AML), demonstrated strong anti-tumor activity and improved survival in four different leukemia mouse models.

The inclusion of a safety-switch using alemtuzumab allows for the rapid termination of cCAR therapy if needed, enhancing the safety profile of this dual-targeting approach against AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. Petrov, JC., Wada, M., Pinz, KG., et al.[2021]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Prospect of CAR T-cell therapy in acute myeloid leukemia. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Anti-CD33 chimeric antigen receptor targeting of acute myeloid leukemia. [2021]

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

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

First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells. [2019]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Compound CAR T-cells as a double-pronged approach for treating acute myeloid leukemia. [2021]