CAR T Cell Therapy for AML and MDS

Recruiting at 1 trial location

Overseen By Amy R. Lankford, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Precigen, Inc

Must not be taking: CD33 CAR T, Monoclonal antibodies

Disqualifiers: APL, CNS leukemic, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

88 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, participants requiring agents other than hydroxyurea to control blast counts within 14 days of study enrollment are excluded, which might imply some restrictions on medication use.

What data supports the effectiveness of the treatment PRGN-3006 T Cells for AML and MDS?

Research shows that CAR T-cell therapy can target and kill cancer cells, with up to 30% of AML patients showing some response, although these responses are often not long-lasting. New strategies are being developed to improve the effectiveness and reduce the side effects of CAR T-cell therapy for AML. ^{1 2 3 4 5}

What is known about the safety of CAR T-cell therapy in humans?

CAR T-cell therapy can cause serious side effects, including cytokine release syndrome (CRS), which can lead to severe symptoms and even life-threatening conditions, and neurotoxicity, which affects the brain. These side effects require careful monitoring and management to ensure patient safety. ^{1 6 7 8 9}

How is the treatment PRGN-3006 T Cells different from other treatments for AML and MDS?

PRGN-3006 T Cells are a type of CAR T cell therapy that targets specific proteins on cancer cells, offering a more precise approach compared to traditional treatments. This therapy is unique because it uses a rapidly switchable platform that allows for better control and safety, reducing the risk of attacking healthy cells. ^{3 4 10 11 12}

What is the purpose of this trial?

This trial is testing a new treatment that uses modified immune cells to target and kill cancer cells in adults with difficult-to-treat or high-risk blood cancers.

Research Team

Amy R. Lankford, PhD

Principal Investigator

Precigen, Inc

Eligibility Criteria

Adults with relapsed or refractory acute myeloid leukemia (AML), MRD-positive AML, or high-risk MDS can join. They must have a certain level of physical fitness, organ function, and no need for oxygen support. Participants should not be pregnant and must agree to contraception. Those who've had bone marrow transplants are eligible if they meet specific conditions.

Inclusion Criteria

I had a stem cell transplant or donor lymphocyte infusion over 3 months ago, with no recent GVHD treatment.

Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) < 3.0 x ULN

Life expectancy ≥ 12 weeks from the time of enrollment

Exclusion Criteria

Participant, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

You have had allergic reactions to drugs similar to cetuximab, which is used to treat EGFR-related conditions.

I haven't had any active cancer except for certain skin cancers or in situ carcinoma in the past year.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of PRGN-3006 to assess safety and tolerability

Up to 6 weeks

Multiple visits (in-person)

Dose Expansion

Participants are treated with the identified dose of PRGN-3006 to evaluate safety and efficacy

Up to 12 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• PRGN-3006 T Cells

Trial Overview The trial is testing PRGN-3006 T Cells, which are modified immune cells designed to target and kill cancer cells in patients with certain types of blood cancers like AML and MDS.

Participant Groups

Group I: Dose Escalation and Dose Expansion of PRGN-3006 Experimental Treatment 1 Intervention

Participants will be treated in dose expansion phase to evaluate the safety and efficacy of the identified dose of PRGN-3006.

Who Is Running the Clinical Trial?

Precigen, Inc

Lead Sponsor

Trials

7

Recruited

300+

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

PGEN Therapeutics, Inc., a subsidiary of Precigen, Inc.

Lead Sponsor

Trials

3

Recruited

200+

Findings from Research

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]

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 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]

Up to 30% of patients with acute myeloid leukemia (AML) show some response to CAR T-cell therapy, but these responses are often not deep or long-lasting, indicating a need for improved treatment strategies.

Common targets for CAR T-cells in AML include CD123, CD33, and CLL-1, but while these therapies can lead to myeloablation and cytokine release syndrome, they rarely cause neurotoxicity, suggesting a relatively safe profile for certain side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia. Cummins, K., Gill, S.[2023]

CAR-T cell therapies, while effective for treating relapsed or refractory blood cancers, can lead to serious adverse effects such as cytokine release syndrome (CRS) and neurotoxicity, which complicate patient management.

The review discusses the pathophysiology and management strategies for these adverse events, and highlights ongoing research aimed at modifying CAR-T cells to reduce toxicity and improve patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies. Yang, C., Nguyen, J., Yen, Y.[2023]

Chimeric antigen receptor T-cell (CART) therapy has achieved impressive complete remission rates of 65% to 90% in pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), marking a significant advancement in treatment.

The introduction of CART therapy has also brought new toxicity profiles and treatment challenges, highlighting the need for standardized toxicity grading systems and innovative management strategies to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-cell Therapy: Current Status and Clinical Outcomes in Pediatric Hematologic Malignancies. Talleur, AC., Myers, R., Annesley, C., et al.[2022]

CD4 is identified as a promising target for CAR-T cell therapy in treating acute myeloid leukemia (AML), as it is expressed in certain AML subtypes but not on normal hematopoietic stem cells, allowing for targeted treatment.

CD4 redirected CAR-T cells effectively eliminated CD4-expressing AML cells in laboratory settings and demonstrated strong anti-leukemic effects in a mouse model, suggesting potential for clinical application in refractory AML cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Targeting of Human Acute Myeloid Leukemia Using CD4-specific Chimeric Antigen Receptor (CAR) T Cells and NK Cells. Salman, H., Pinz, KG., Wada, M., et al.[2020]

References

1. 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]

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

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

Chimeric antigen receptor T cells for acute myeloid leukemia. [2023]

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

Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia. [2023]

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

Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies. [2023]

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

Chimeric Antigen Receptor T-cell Therapy: Current Status and Clinical Outcomes in Pediatric Hematologic Malignancies. [2022]

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

Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Immune Cell-Based Therapies to Eradicate High-Risk Acute Myeloid Leukemia. [2021]

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

Evaluation of switch-mediated costimulation in trans on universal CAR-T cells (UniCAR) targeting CD123-positive AML. [2021]

11. Australia pubmed.ncbi.nlm.nih.gov

Preclinical Targeting of Human Acute Myeloid Leukemia Using CD4-specific Chimeric Antigen Receptor (CAR) T Cells and NK Cells. [2020]

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

Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells. [2022]