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

Recruiting at 3 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ARD103 (a CAR-T therapy) for individuals with acute myeloid leukemia or myelodysplastic syndrome, particularly if the disease has returned or not responded to previous treatments. The trial aims to determine the safety and effectiveness of ARD103 for these conditions. It consists of two phases: the first phase identifies the appropriate dose, and the second phase evaluates the treatment's efficacy. Individuals diagnosed with relapsed or refractory acute myeloid leukemia or myelodysplastic syndrome with at least 5% bone marrow blasts may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that ARD103 is likely to be safe for humans?

Research shows that ARD103 CAR-T therapy is still in the early stages of testing for safety in treating acute myeloid leukemia and myelodysplastic syndrome. While promising, there is limited information on its safety. The trial tests different doses to find the safest amount for patients.

As a Phase 1/2 trial, researchers are determining the best dose and monitoring for side effects. Participants are closely observed to assess their response to the treatment. Common concerns with CAR-T therapies include side effects like fever or tiredness, but specific information on ARD103 is not yet available.

CAR-T therapies like ARD103 have been used for other conditions, suggesting some level of safety, but each new treatment can differ. It is important to consult a healthcare provider to understand potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for acute myeloid leukemia and myelodysplastic syndrome?

Unlike the standard treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), which often include chemotherapy and stem cell transplants, ARD103 CAR-T therapy uses a novel approach called chimeric antigen receptor T-cell (CAR-T) therapy. This cutting-edge treatment involves reprogramming a patient's own T-cells to specifically target and destroy cancer cells, which offers a more personalized and precise attack against the disease. Researchers are excited because CAR-T therapy has the potential to provide longer-lasting remissions with potentially fewer side effects, as it harnesses the body's immune system to fight the cancer more effectively.

What evidence suggests that ARD103 might be an effective treatment for acute myeloid leukemia and myelodysplastic syndrome?

Research has shown that CAR-T therapy, such as ARD103, could be promising for treating cancers like acute myeloid leukemia and myelodysplastic syndrome. CAR-T therapy modifies a patient’s T-cells (a type of immune cell) to enable them to locate and destroy cancer cells. In past studies with similar CAR-T treatments, patients experienced significant tumor shrinkage and longer survival times. While specific results for ARD103 are still being gathered in this trial, the technology has shown promise in treating other challenging blood cancers. Early results in similar cases suggest that ARD103 might help in finding and eliminating cancer cells in these conditions. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06680752

NCT06680752 | Clinical Study of ARD103 CAR-T Therapy ... 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 ...

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/553235

Clinical Study of ARD103 CAR-T Therapy for Patients With R ... 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 ...

3. clinicaltrial.be clinicaltrial.be/en/details/458152?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

Clinical Study of ARD103 CAR-T Therapy for Patients With... ... Efficacy of ARD103 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome. NCT06680752. NCT. clinicaltrials ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/553235

Clinical Study of ARD103 CAR-T Therapy for Patients With R/R ... 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06906380

A Long-term Follow-up Study of Patients With ARD103 ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

6. trial.medpath.com trial.medpath.com/clinical-trial/f82cd9df9cab2b3e/nct06680752-safety-efficacy-ard103-leukemia-syndrome

Clinical Study of ARD103 CAR-T Therapy for Patients With R ... 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 ...