Gene Modified T-cells for Blood Disorders

Recruiting at 10 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bellicum Pharmaceuticals

Must not be taking: Immunosuppressants

Disqualifiers: Severe cardiovascular, Active infections, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate pediatric patients with malignant or non-malignant blood cell disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa and beta cells that comes from a partially matched family donor. The study will assess whether immune cells, called T cells, from the family donor, that are specially grown in the laboratory and given back to the patient along with the stem cell transplant can help the immune system recover faster after transplant. As a safety measure these T cells have been programmed with a self-destruct switch so that they can be destroyed if they start to react against tissues (graft versus host disease).

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment BPX-501 T cells, Rimiducid, AP1903 for blood disorders?

Research on gene-modified T cells, like those used in BPX-501, shows promise in treating blood disorders by enhancing the immune system's ability to target and destroy diseased cells. Studies have demonstrated that genetically engineered T cells can effectively reduce tumor growth and improve survival in animal models, suggesting potential benefits for patients with blood disorders. ^{1 2 3 4 5}

Is gene-modified T-cell therapy generally safe for humans?

Gene-modified T-cell therapies, like those using the Sleeping Beauty system, have shown antileukemic activity with minimal severe toxicities, such as mild cytokine-release syndrome (a reaction where the immune system releases too many proteins into the blood too quickly). Safety measures, like the iCasp9 safety switch, are being developed to manage potential risks, and ongoing trials are essential to ensure these treatments are safe for broader use. ^{2 3 6 7 8}

How is the treatment BPX-501 T cells unique for blood disorders?

BPX-501 T cells are unique because they involve genetically modifying T cells to enhance their ability to target specific disease cells, using a non-viral method called the Sleeping Beauty transposon system. This approach is more cost-effective and efficient compared to traditional viral methods, and it allows for the stable integration of therapeutic genes into T cells, potentially improving their effectiveness in treating blood disorders. ^{2 3 5 9 10}

Research Team

Bellicum Pharmaceuticals

Principal Investigator

Bellicum Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for children and young adults (1 month to <26 years old) with certain life-threatening blood disorders or cancers, who are eligible for a stem cell transplant but don't have a fully matched donor available. Participants need to be in relatively good health aside from their primary condition, with major organs functioning well and a reasonable life expectancy.

Inclusion Criteria

I have a non-cancerous condition that could be cured with a transplant.

I don't have a matching donor or my disease is progressing too quickly to wait for one.

I am between 1 month and 26 years old.

Exclusion Criteria

I've received a specific cell treatment and need approval for a new infusion.

My liver and kidney functions are within normal limits.

I do not have severe heart problems like chronic arrhythmias, heart failure, or poor heart pump function.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a TCR alpha beta depleted graft infusion with addback of BPX-501 T cells, and potentially Rimiducid if GvHD occurs

24 months

Follow-up

Participants are monitored for safety, immune reconstitution, and incidence of GvHD after treatment

24 months

Extension

Long-term monitoring for disease-free survival and relapse

12-24 months

Treatment Details

Interventions

• BPX-501 T cells
• Rimiducid

Trial Overview The study tests genetically modified T-cells called BPX-501 following a special type of stem cell transplant from partially matched family donors. The goal is to see if these engineered T-cells can help rebuild the immune system more quickly while having the ability to be turned off if they cause harmful reactions.

Participant Groups

Group I: BPX-501 T cells and Rimiducid Experimental Treatment 2 Interventions

TCR alpha beta depleted graft infusion with addback of BPX-501 T cells. Rimiducid: Dimerizer drug administered to subjects who present with Grade I-IV acute GVHD with inadequate response to steroids within 48 hours of treatment or mild to severe chronic GVHD with inadequate response to steroids within 7 days of treatment.

Who Is Running the Clinical Trial?

Bellicum Pharmaceuticals

Lead Sponsor

Trials

28

Recruited

1,400+

Findings from Research

In a phase I/II trial involving 13 patients with B cell acute lymphoblastic leukemia (B-ALL) who relapsed after stem cell transplantation, donor-derived CD19 CAR T cells showed promising results, with 6 out of 7 patients receiving the highest doses achieving complete remission (CR) or CR with incomplete blood count recovery (CRi) by day 28.

The CAR T cell therapy demonstrated a favorable safety profile, with only mild cytokine-release syndrome reported and no severe toxicities such as graft-versus-host disease or neurotoxicity, indicating that this approach could be a viable treatment option for relapsed B-ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities. Magnani, CF., Gaipa, G., Lussana, F., et al.[2021]

Adoptive T-cell therapy shows promise for treating various cancers and infections, but safety concerns remain due to potential on-target and off-target toxicities, which can sometimes be fatal.

The inducible caspase 9 (iCasp9) safety switch offers a solution by allowing for the rapid elimination of modified T cells if adverse effects occur, enhancing the safety of T-cell therapies, especially in cases like graft-versus-host disease in stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy: adverse events and safety switches. Tey, SK.[2022]

The study demonstrated that using CRISPR/Cas9 to knock out the TCR gene in ARI-0001 CAR-T cells can effectively disrupt the TCR without significantly altering the T cell phenotype, achieving over 80% efficiency.

While this method shows promise for creating allogeneic CAR-T cells with maintained anti-tumor activity, there are potential safety risks due to possible large deletions in the genome that require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma. Maldonado-Pérez, N., Tristán-Manzano, M., Justicia-Lirio, P., et al.[2022]

References

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

Gene editing to enhance the efficacy of cancer cell therapies. [2023]

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

Challenges in T cell receptor gene therapy. [2023]

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

Sleeping Beauty transposon-mediated engineering of human primary T cells for therapy of CD19+ lymphoid malignancies. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Off the shelf T cell therapies for hematologic malignancies. [2021]

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

A new approach to gene therapy using Sleeping Beauty to genetically modify clinical-grade T cells to target CD19. [2021]

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

Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities. [2021]

7. Australia pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy: adverse events and safety switches. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of universal (TCRKO) ARI-0001 CAR-T cells for the treatment of B-cell lymphoma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

T-cell gene therapy. [2019]

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

Genetic modification of T lymphocytes for adoptive immunotherapy. [2017]