CAR T Cell Therapy for AML and MDS

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PRGN-3006 CAR T cells, which are specially modified immune cells designed to target and kill cancer cells. The goal is to determine the safest and most effective dose for individuals with certain blood cancers, specifically relapsed or hard-to-treat acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Suitable candidates have AML or MDS that hasn't responded to treatment and have a matched bone marrow donor. Participants should not rely on oxygen therapy and must understand the trial requirements. This study aims to offer a new treatment option for these challenging conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this innovative therapy.

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.

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

Research has shown that PRGN-3006 T cells are safe and well-tolerated in early studies. In one study, 24 patients with conditions like acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) received the treatment, and it was generally safe. No unexpected severe side effects occurred. This suggests that PRGN-3006 has a promising safety profile. However, as this is an early-stage study, the main goal is to find the best dose and monitor any side effects. Overall, the early results are encouraging for those considering joining a trial with PRGN-3006. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

PRGN-3006 T Cells are unique because they utilize CAR T cell therapy to specifically target and destroy cancer cells in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Unlike traditional treatments such as chemotherapy, which attack both healthy and cancerous cells, CAR T cell therapy involves engineering a patient's own immune cells to recognize and attack cancer cells, potentially reducing damage to healthy cells. This targeted approach could lead to more effective treatments with fewer side effects, making researchers hopeful about its potential to improve outcomes for patients with these challenging conditions.

What evidence suggests that PRGN-3006 T Cells might be an effective treatment for AML and MDS?

Research shows that PRGN-3006 T cells could help treat relapsed or hard-to-treat acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). These T cells are specially designed to find and destroy cancer cells by recognizing a specific protein on them. Early studies have shown positive results, with some patients experiencing a reduction in cancer cells after treatment. The treatment also includes a substance called IL-15, which helps the T cells live longer and function more effectively. Although this therapy is still being tested in this trial, early data suggests it might be effective for some patients with these challenging conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

Amy R. Lankford, PhD

Principal Investigator

Precigen, Inc

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/10313/489552/Phase-1-1b-Safety-Study-of-Prgn-3006-Ultracar-T-in

Phase 1/1b Safety Study of Prgn-3006 Ultracar-T in Patients ... Results: As of July 15, 2022 data cut-off, 24 pts have been treated in C1 (n=10) and C2 (n=14). The study enrolled 20 r/r AML, 1 CMML, and 3 MDS ...

2. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-announces-positive-interim-phase-1-data-prgn-3006

Press Releases Precigen Announces Positive Interim Phase 1 Data for PRGN-3006 UltraCAR-T® in Relapsed or Refractory Acute Myeloid Leukemia. Dec 13, 2021.

3. mayo.edu mayo.edu/research/clinical-trials/cls-20523796

PRGN-3006 Adoptive Cellular Therapy for CD33-Positive ... The purpose of this study is to determine the safety and best dose of PRGN-3006 T Cells to treat relapsed/refractory Acute Myeloid Leukemia and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10164930/

Outcomes with chimeric antigen receptor t-cell therapy in ... We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121028135

Clinical Phase 1/1b Safety Study of Prgn-3006 Ultracar-T in ... PRGN-3006 UltraCAR-T are engineered using non-viral gene delivery to simultaneously express CD33 CAR, membrane bound IL-15 (mbIL15) and kill ...

6. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-presents-new-data-supporting-safety-clinical-activity

Press Releases PRGN-3006 has been safe and well-tolerated to date -. - Case study demonstrated persistence of PRGN-3006 administered without prior ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03826082/

Clinical Trial: NCT03826082 This study is to determine the safety and best dose of PRGN-3006 T Cells. Related Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes. Recruiting ...