UltraCAR-T Therapy for Leukemia and Breast Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Warfarin, Immunosuppressants, others

Disqualifiers: Burkitt lymphoma, 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 explores a new treatment called PRGN-3007 UltraCAR-T cells, a type of cell therapy, to determine its effectiveness for certain types of leukemia and breast cancer. It targets conditions such as chronic lymphocytic leukemia, mantle cell lymphoma, acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and triple-negative breast cancer. The study divides participants into groups to test different doses and identify the safest and most effective one. Suitable candidates have specific types of these cancers and face challenges like persistent symptoms despite previous treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop certain medications before joining. You must be off cytotoxic chemotherapy, radiation therapy, and some other treatments for a specific time before starting the trial. Check with the trial team to see if your current medications are affected.

Is there any evidence suggesting that PRGN-3007 UltraCAR-T cells are likely to be safe for humans?

Research shows that PRGN-3007 UltraCAR-T cells have a promising safety record. Studies on similar treatments, such as PRGN-3005 and PRGN-3006, indicate they are generally well-tolerated. These treatments often perform better at higher doses without causing major side effects.

For PRGN-3007, early results suggest it is safe for treating both blood cancers and solid tumors, including certain breast cancers. Although specific details about PRGN-3007 are not provided, its advancement to the current trial phase indicates it has demonstrated some safety in humans.

PRGN-3007 remains under testing, so current safety information is based on observations so far. As trials progress, more detailed safety data will become available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

PRGN-3007 is unique because it uses UltraCAR-T technology, which is a new approach to treating leukemia and breast cancer. Unlike conventional treatments that rely on chemotherapy or targeted drugs, UltraCAR-T modifies a patient's own immune cells to better target and fight cancer cells. This personalized treatment has the potential to be more effective and less toxic than traditional options. Researchers are excited because UltraCAR-T could offer faster and more durable responses, giving patients a promising new avenue for treatment.

What evidence suggests that this trial's treatment could be effective for leukemia and breast cancer?

Research shows that PRGN-3007 UltraCAR-T cells have potential in early studies for treating both blood cancers and solid tumors. The trial will evaluate PRGN-3007 in different groups: participants with hematologic malignancies and those with solid tumors. This treatment targets a protein called ROR1, found on some cancer cells. By attacking these cells, PRGN-3007 aims to slow or stop cancer growth. Early results are promising, suggesting the treatment could work against certain types of leukemia, lymphoma, and breast cancer. These initial findings offer hope, but ongoing studies must provide more information to understand its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Javier Pinilla-Ibarz, MD, PhD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

Adults with certain blood cancers or solid tumors, like leukemia and breast cancer, who are in fairly good health (ECOG score of 0 or 1) and expected to live at least 12 weeks can join. They must not be pregnant, agree to use birth control, understand the study's consent form, have no serious lung/cardiac issues or infections, no recent major surgeries or other cancer treatments within specific time frames.

Inclusion Criteria

You are expected to live for at least 12 weeks from the time you join the study.

I am mostly active and can care for myself.

I am not pregnant and willing to use birth control during and after treatment.

Exclusion Criteria

I cannot receive certain chemotherapy due to health risks.

I do not have an immune deficiency, active autoimmune disease needing strong medication, or recent immunosuppressive therapy.

I had a stem cell transplant or donor lymphocyte infusion less than 6 months ago, or I currently have severe graft versus host disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Lymphodepletion

Participants undergo leukapheresis followed by lymphodepletion with fludarabine and cyclophosphamide

3-5 days

Dose Escalation

Participants receive PRGN-3007 in 3 dose levels to determine Maximum Tolerated Dose (MTD) using a 3+3 escalation design

Up to 12 months

Dose Expansion

Participants receive PRGN-3007 at the dose level determined to be the Maximum Tolerated Dose (MTD)

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• PRGN-3007

Trial Overview The trial is testing PRGN-3007 UltraCAR-T cells combined with Fludarabine and Cyclophosphamide chemotherapy to see if they're effective against ROR1-positive malignancies including various leukemias, lymphomas, and triple negative breast cancer.

How Is the Trial Designed?

Group I: Phase 1b Dose Expansion (Group B) Experimental Treatment 2 Interventions

Participants from group B (solid tumors) will undergo leukapheresis followed by lymphodepletion and infusion of PRGN-3007. Lymphodepletion will include 2 days of cyclophosphamide (500 mg/m\^2) prior to study day 0.Participants will then receive PRGN-3007 at the dose level determined to be the Maximum Tolerated Dose (MTD) in the dose escalation portion of the study.

Group II: Phase 1b Dose Expansion (Group A) Experimental Treatment 3 Interventions

Participants from group A (hematologic malignancies) will undergo leukapheresis followed by lymphodepletion and infusion of PRGN-3007. Lymphodepletion will include 3 days of treatment with fludarabine (30 mg/m\^2) and cyclophosphamide (500 mg/m\^2) prior to study day 0. Participants will then receive PRGN-3007 at the dose level determined to be the Maximum Tolerated Dose (MTD) in the dose escalation portion of the study.

Group III: Phase 1 Dose Escalation (Group B) Experimental Treatment 2 Interventions

Participants from group B (solid tumors) will undergo leukapheresis followed by lymphodepletion and infusion of PRGN-3007. Lymphodepletion will include 2 days of cyclophosphamide (500 mg/m\^2) prior to study day 0. Participants will then receive PRGN-3007 in 3 dose levels beginning at Dose Level 1, using a standard 3+3 escalation design to determine Maximum Tolerated Dose (MTD). The target maximum doses infused at each dose level is: Dose Level 1: 1x10\^6 cells/kg Dose Level 2: 3x10\^6 cells/kg Dose Level 3: 1x10\^7 cells/kg

Group IV: Phase 1 Dose Escalation (Group A) Experimental Treatment 3 Interventions

Participants from group A (hematologic malignancies) will undergo leukapheresis followed by lymphodepletion and infusion of PRGN-3007. Lymphodepletion will include 3 days of treatment with fludarabine (30 mg/m\^2) and cyclophosphamide (500 mg/m\^2) prior to study day 0. Participants will then receive PRGN-3007 in 3 dose levels beginning at Dose Level 1, using a standard 3+3 escalation design to determine Maximum Tolerated Dose (MTD). The target maximum doses infused at each dose level is: Dose Level 1: 1x10\^6 cells/kg Dose Level 2: 3x10\^6 cells/kg Dose Level 3: 1x10\^7 cells/kg

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Precigen, Inc

Industry Sponsor

Trials

7

Recruited

300+

Published Research Related to This Trial

In a phase-1/2 trial involving 13 adult patients with refractory acute lymphoblastic leukemia, third-generation CAR T cells (CARTs) demonstrated promising efficacy, with 80% of evaluable patients achieving complete remission, including 50% with no detectable residual disease.

The treatment was associated with remarkably low toxicity, as none of the patients experienced severe side effects like neurotoxicity or high-grade cytokine release syndrome, indicating a favorable safety profile for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. Schubert, ML., Schmitt, A., Hückelhoven-Krauss, A., et al.[2023]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

CAR T-cell immunotherapy, which involves genetically modifying T cells to target cancer cells, has shown promising results, especially in treating B-cell malignancies with several patients achieving complete and durable responses.

Current research is expanding CAR T-cell therapy to solid tumors, specifically targeting members of the ErbB family, indicating a potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ErbB-targeted CAR T-cell immunotherapy of cancer. Whilding, LM., Maher, J.[2022]

Allogeneic stem cell transplant is currently the only curative option for T-cell malignancies, but it carries significant risks and toxicities, highlighting the need for safer alternatives.

UCART7, a novel CAR-T therapy targeting the CD7 marker in T-cell malignancies, shows promise for treating relapsed T-cell acute lymphoblastic leukemia (T-ALL) and may offer a new option for patients with limited effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells (CAR-T) for the treatment of T-cell malignancies. Cooper, ML., DiPersio, JF.[2020]

Chimeric antigen receptor (CAR) T-cell therapy has shown significant efficacy in treating refractory leukemia, particularly with CD19-targeting CAR-T cells leading to sustained responses in patients with relapsed acute lymphoblastic leukemia.

Recent advancements in CAR-T cell design, including improved intracellular activating domains and viral vector transduction, have enhanced the effectiveness of these therapies and expanded the range of potential leukemic antigens for targeting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T therapy for leukemia: progress and challenges. Wang, X., Xiao, Q., Wang, Z., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05694364?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(precigen))&rank=6

Dose Escalation/Dose Expansion Study of PRGN-3007 ... The purpose of the study is to find out if an investigational drug called PRGN-3007 UltraCAR-T cells (PRGN-3007 T cells) can help people with ROR1-positive ...

2. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-announces-further-advancement-ultracar-tr-platform

Precigen Announces Further Advancement of UltraCAR-T ... The Phase 1/1b clinical trial is an open-label study designed to evaluate the safety and efficacy of PRGN-3007 in patients with advanced ROR1+ ...

3. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-achieves-significant-clinical-progress-ultracar-tr-and

Precigen Achieves Significant Clinical Progress for ... Today's R&D Day highlights the most significant clinical data presented for the UltraCAR-T and AdenoVerse platforms to date.

4. researchgate.net researchgate.net/publication/356481332_Preclinical_Evaluation_of_Prgn-3007_a_Non-Viral_Multigenic_Autologous_ROR1_Ultracar-T_R_Therapy_with_Novel_Mechanism_of_Intrinsic_PD-1_Blockade_for_Treatment_of_Hematological_and_Solid_Cancers

Preclinical Evaluation of Prgn-3007, a Non-Viral ... PRGN-3007 UltraCAR-T started its Phase-1 clinical trial for ROR1-positive hematological malignancies and solid tumors, including triple ...

5. prnewswire.com prnewswire.com/news-releases/precigen-announces-further-advancement-of-ultracar-t-platform-with-first-patient-dosed-in-phase-11b-dose-escalationdose-expansion-study-of-prgn-3007-in-advanced-ror1-hematological-and-solid-tumors-301784205.html

Precigen Announces Further Advancement of UltraCAR-T ... The Phase 1/1b clinical trial is an open-label study designed to evaluate the safety and efficacy of PRGN-3007 in patients with advanced ROR1+ ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-00599

UltraCAR-T Cells (PRGN-3007) in Treating patients with ... This phase I/Ib trial test the safety, side effects, and best dose of ultraCAR-T cells (PRGN-3007) in treating patients with blood (hematologic) or solid ...

7. 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 ... Complete Phase 1 dose escalation data along with updated safety, efficacy, PK/PD and cytokine data will be presented at the meeting. The ...