Allogeneic CAR-T Cell Therapy for B-Cell Cancer

Recruiting at 10 trial locations

Overseen By Angie Schinkel

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Poseida Therapeutics, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Pregnancy, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

120 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1 study comprised of open-label, dose escalation and expansion cohort study of P-CD19CD20-ALLO1 allogeneic T stem cell memory (Tscm) CAR-T cells in subjects with relapsed/refractory B cell malignancies

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have received certain anti-cancer medications, monoclonal antibody therapy, or immunosuppressive medications within specific timeframes before starting the trial. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment P-CD19CD20-ALLO1 for B-cell cancer?

Research shows that similar allogeneic CAR T-cell therapies targeting CD19 have been effective in causing regression of B-cell cancers, even in cases resistant to standard treatments. Additionally, preclinical studies of dual-targeting CAR T cells (targeting CD20 and CD22) have shown strong activity against B-cell cancers, suggesting potential effectiveness for P-CD19CD20-ALLO1. ^{1 2 3 4 5}

Is allogeneic CAR-T cell therapy for B-cell cancer safe?

Allogeneic CAR-T cell therapy for B-cell cancer has shown a generally good safety profile in clinical trials. Some patients experienced mild to moderate side effects like cytokine release syndrome (a reaction that can cause fever and low blood pressure) and neurotoxicity (affecting the nervous system), but these were manageable. Serious adverse events were rare, and no cases of graft-versus-host disease (a condition where donor cells attack the recipient's body) were reported. ^{4 6 7 8 9}

How is the treatment P-CD19CD20-ALLO1 different from other treatments for B-cell cancer?

P-CD19CD20-ALLO1 is unique because it uses allogeneic (donor-derived) CAR-T cells that target both CD19 and CD20 proteins on B-cells, potentially reducing the risk of disease relapse without causing graft-versus-host disease, a common complication in similar therapies. ^{2 3 4 10 11}

Research Team

Rajesh Belani, MD

Principal Investigator

Vice President, Clinical Development

Eligibility Criteria

Adults (≥18 years) with certain B cell malignancies like DLBCL, FL, MCL, MZL, PMBCL or CLL that have relapsed or are not responding to treatment. They must have tried specific therapies and meet health criteria including organ function and blood counts. Pregnant individuals, those with autoimmune diseases or active infections are excluded.

Inclusion Criteria

My lymphoma is measurable by specific medical criteria.

Must have a negative serum pregnancy test

It has been at least 90 days since my stem cell transplant.

Exclusion Criteria

Is pregnant or lactating

Has inadequate venous access

I have another type of cancer that is currently active.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive a lymphodepletion therapy regimen before administration of allogeneic CAR-T cells

1 week

Treatment

Participants receive a single dose of P-CD19CD20-ALLO1 CAR-T cells following conditioning chemotherapy

4 weeks

Weekly visits for safety and response assessments

Follow-up

Participants are monitored for safety, tolerability, and response after treatment

36 months

Regular visits for monitoring adverse events and response

Long-term follow-up

Participants are monitored for long-term effects and overall survival

15 years

Treatment Details

Interventions

• P-CD19CD20-ALLO1

Trial Overview The trial is testing P-CD19CD20-ALLO1 allogeneic CAR-T cells along with Rimiducid in patients with B cell cancers that came back or didn't respond after treatment. It's a Phase 1 study where doses will be increased gradually to find the safest dose that works.

Participant Groups

Group I: P-CD19CD20-ALLO1 CAR-T Cells (Arm S) Experimental Treatment 2 Interventions

P-CD19CD20-ALLO1 following conditioning chemotherapy regimen S. Rimiducid may be administered.

Group II: P-CD19CD20-ALLO1 CAR-T Cells (Arm LD 750) Experimental Treatment 2 Interventions

P-CD19CD20-ALLO1 following conditioning chemotherapy regimen LD 750. Rimiducid may be administered.

Group III: P-CD19CD20-ALLO1 CAR-T Cells (Arm LD 1000) Experimental Treatment 2 Interventions

P-CD19CD20-ALLO1 following conditioning chemotherapy regimen LD 1000. Rimiducid may be administered.

Who Is Running the Clinical Trial?

Poseida Therapeutics, Inc.

Lead Sponsor

Trials

6

Recruited

780+

Roche-Genentech

Industry Sponsor

Trials

27

Recruited

3,800+

Findings from Research

The study introduces a dual allogeneic CAR T cell targeting both CD20 and CD22, which shows strong and sustained activity against B-cell non-Hodgkin lymphoma (B-NHL) in laboratory and animal models, addressing the issue of tumor antigen escape.

This new approach offers a promising alternative to traditional autologous CAR T cell therapies by potentially providing 'off-the-shelf' treatment options that can effectively target tumors with varying levels of CD20 and CD22 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evidence of an Allogeneic Dual CD20xCD22 CAR to Target a Broad Spectrum of Patients with B-cell Malignancies. Aranda-Orgilles, B., Chion-Sotinel, I., Skinner, J., et al.[2023]

In a study of 35 patients with relapsed B-cell acute lymphoblastic leukemia after allogeneic stem cell transplantation, 85.7% achieved complete remission after receiving CD19-targeted CAR T cell therapy, indicating high initial efficacy.

However, the long-term outcomes were concerning, with a recurrence rate of 68.3% at 18 months and an overall survival rate of only 30.0%, suggesting that additional treatments may be necessary to improve long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. Chen, YH., Zhang, X., Cheng, YF., et al.[2021]

Engineered CD19-chimeric antigen receptor (CAR) T cells can safely target and treat CD19-positive B-cell malignancies that have relapsed after allogeneic stem cell transplantation.

This study highlights the potential of using donor-derived allogeneic T cells in combination with CAR technology to improve treatment outcomes for patients with these types of cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donating used CARs. Rapoport, AP.[2021]

In a clinical trial involving 10 patients with B-cell malignancies that persisted after allogeneic hematopoietic stem cell transplantation, treatment with genetically modified T cells targeting the CD19 antigen led to tumor regressions in three patients, including one achieving complete remission.

The study demonstrated that these allogeneic anti-CD19-CAR T cells can effectively target and reduce B-cell malignancies without causing graft-versus-host disease (GVHD), a common complication in such treatments, indicating a promising safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Kochenderfer, JN., Dudley, ME., Carpenter, RO., et al.[2023]

In a study involving nine patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) and low donor chimerism after allogeneic stem cell transplant, autologous anti-CD19 CAR T cell therapy successfully restored complete donor chimerism in vitro after 12 days of culture.

The therapy showed strong cytotoxic effects against leukemia cells, with most patients experiencing mild cytokine release syndrome as the main adverse event, and two out of three treated patients achieving complete response without acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Level Donor Chimerism of CD19 CAR-T Cells Returned to Complete Donor Chimerism in Patients with Relapse After Allo-Hematopoietic Stem Cell Transplant. Li, Q., Mu, J., Yuan, J., et al.[2022]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

In a study of 43 patients with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) who relapsed after an allotransplant, 79% achieved complete remission after receiving allogeneic anti-CD19 CAR-T cells, indicating high efficacy of this treatment.

While the therapy was effective, it was associated with a high incidence of cytokine release syndrome (CRS) in 88% of patients, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. Zhang, C., Wang, XQ., Zhang, RL., et al.[2021]

In a phase 1 study involving 12 pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), the autologous CD19-CAR T-cell therapy was well tolerated, with low rates of cytokine release syndrome (6 patients) and neurotoxicity (3 patients).

75% of the patients achieved a minimal residual disease-negative complete response in the bone marrow, although higher disease burden before treatment was linked to more side effects and lower response rates, emphasizing the importance of pre-infusion disease status on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Talleur, AC., Qudeimat, A., Métais, JY., et al.[2022]

Allogeneic CAR+ Vδ1 γδ T cells targeting the CD20 antigen showed promising antitumor activity against B-cell tumors in preclinical studies, demonstrating both innate and adaptive immune responses.

These engineered T cells did not cause graft-versus-host disease in immunodeficient mice, suggesting a safer profile for potential clinical use in patients with B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic CD20-targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B-cell lymphoma models. Nishimoto, KP., Barca, T., Azameera, A., et al.[2022]

Infusing donor-derived T cells that are engineered to target the B-cell antigen CD19 can enhance the antitumor effect in patients with high-risk B-cell malignancies after stem-cell transplantation, while minimizing the risk of graft-versus-host disease.

The study demonstrated that T cells could be modified to reduce alloreactive responses through a process called alloanergization, allowing them to maintain their cancer-fighting abilities without increasing toxicity, which could lead to better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining CD19 redirection and alloanergization to generate tumor-specific human T cells for allogeneic cell therapy of B-cell malignancies. Davies, JK., Singh, H., Huls, H., et al.[2021]

References

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

Preclinical Evidence of an Allogeneic Dual CD20xCD22 CAR to Target a Broad Spectrum of Patients with B-cell Malignancies. [2023]

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

Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation. [2021]

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

Donating used CARs. [2021]

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

Donor-derived CD19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. [2023]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Low Level Donor Chimerism of CD19 CAR-T Cells Returned to Complete Donor Chimerism in Patients with Relapse After Allo-Hematopoietic Stem Cell Transplant. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

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

Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. [2021]

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

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Allogeneic CD20-targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B-cell lymphoma models. [2022]

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

Combining CD19 redirection and alloanergization to generate tumor-specific human T cells for allogeneic cell therapy of B-cell malignancies. [2021]