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

3 Participants Needed

Trial Summary

What is the purpose of this trial?

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 hematologic chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and solid tumor triple negative breast cancer (TNBC) malignancies.

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.

What data supports the effectiveness of the treatment PRGN-3007 in the UltraCAR-T Therapy for Leukemia and Breast Cancer?

CAR T-cell therapy, which involves modifying T cells to target cancer cells, has shown promising results in treating blood cancers like B-cell acute lymphoblastic leukemia, with high remission rates. This suggests potential effectiveness for similar therapies like PRGN-3007 in treating leukemia and possibly breast cancer. ^{1 2 3 4 5}

What makes the UltraCAR-T treatment PRGN-3007 unique for leukemia and breast cancer?

UltraCAR-T therapy, like PRGN-3007, is unique because it involves genetically modifying T cells to specifically target cancer cells, offering a personalized approach that can potentially lead to complete remission in cases where traditional treatments have failed. This therapy is part of a new wave of immunotherapies that use chimeric antigen receptors (CARs) to enhance the body's immune response against cancer. ^{3 4 6 7 8}

Research Team

Javier Pinilla-Ibarz, MD, PhD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Phase I Trial of Anti-PSMA Designer CAR-T Cells in Prostate Cancer: Possible Role for Interacting Interleukin 2-T Cell Pharmacodynamics as a Determinant of Clinical Response. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy in oncology - Pipeline at a glance: Analysis of the ClinicalTrials.gov database. [2022]

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

ErbB-targeted CAR T-cell immunotherapy of cancer. [2022]

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

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

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

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. [2023]

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells (CAR-T) for the treatment of T-cell malignancies. [2020]

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

CAR-T therapy for leukemia: progress and challenges. [2018]