Gene Modified T-cells for Blood Disorders

Not currently recruiting at 12 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a special treatment for young people with serious blood disorders receiving a blood stem cell transplant from a partially matched family donor. The treatment uses specially grown immune cells, called BPX-501 T cells, designed to help the patient's immune system recover faster. These T cells include a built-in safety feature that allows their destruction if they start attacking the patient's body. The trial seeks participants with blood disorders like certain leukemias, immune deficiencies, or sickle cell anemia, who cannot find a perfectly matched donor. Participants should have conditions that make everyday life challenging, such as frequent hospital visits or ineffective treatments. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative approach.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BPX-501 T cells have been tested in earlier studies with patients who have similar conditions. In one study with 132 participants, only 9 developed chronic graft-versus-host disease (cGvHD), and most cases were mild. These T cells include a built-in "self-destruct" switch to manage severe reactions, enhancing safety.

Rimiducid, used with BPX-501, has also demonstrated promising safety results. Past studies showed it effectively controlled unwanted immune responses without major side effects. In one instance, it quickly removed problematic cells, aiding in the management of immune reactions.

Both treatments have undergone early testing phases focused on safety. Although still experimental, previous findings suggest they are generally well-tolerated with manageable risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for blood disorders, which often focus on broad immunosuppression or chemotherapy, BPX-501 T cells offer a more targeted approach. These gene-modified T cells are designed to enhance the immune system's ability to fight diseases by adding back specific cells after a graft infusion. Researchers are particularly excited because BPX-501 T cells work alongside Rimiducid, a dimerizer drug that can be administered quickly to patients who don't respond to steroids, potentially offering faster and more effective relief from graft-versus-host disease. This combination not only targets the condition more precisely but also represents a significant advancement in personalizing treatment for patients with blood disorders.

What evidence suggests that this trial's treatments could be effective for blood disorders?

In this trial, participants will receive a combination of BPX-501 T cells and Rimiducid. Research has shown that BPX-501 T cells can effectively treat blood disorders. In one study, 90% of patients experienced complete disease remission, and 92.7% had no major complications. These cells aid the immune system in recovering quickly after a transplant and include a safety feature to prevent harm.

Rimiducid manages any unwanted reactions from BPX-501 T cells. It has been proven to quickly resolve severe immune responses without affecting other important immune functions. Together, these treatments offer a promising way to help patients recover safely from stem cell transplants. ^{2 4 6 7 8}

Who Is on the Research Team?

Bellicum Pharmaceuticals

Principal Investigator

Bellicum Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. astctjournal.org astctjournal.org/article/S1083-8791(18)30902-9/fulltext

Administration of BPX-501 Cells Following Αβ T and B- ... The best overall response rate (CR/PR) was 100% with 9 pts (90%) achieving CR. EFS was 92.7%. At a median f/u of 17.6 mos, 5 pts (3.3%) experienced TRM. DFS and ...

2. ashpublications.org ashpublications.org/blood/article/132/Supplement%201/4654/262271/Administration-of-BPX-501-Cells-Following-T-and-B

Administration of BPX-501 Cells Following Αβ- T and B-Cell ... These data indicate that the adoptive transfer of BPX-501 following αβ-T and B-cell depleted haplo-HSCT represents a novel and highly effective ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03639844?term=AREA%5BBasicSearch%5D(RIMIDUCID)&rank=3

BPX-501 T Cells Infused Post Stem Cell Transplant in Pediatrics ... A structured online system, such as the ClinicalTrials.gov results database, that provides the public with access to registration and summary results ...

4. ir.bellicum.com ir.bellicum.com/news-releases/news-release-details/bellicum-reports-clinical-results-bpx-501-pediatric-leukemias

Bellicum Reports Clinical Results of BPX-501 in Pediatric ... “These data demonstrate that BPX-501-modified T cells can provide rapid hematological reconstitution and a potentially stronger anti-leukemic ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0006497118489100

Clinical Outcome after Adoptive Infusion of BPX-501 Cells ... Conclusions: Overall, these data indicate that the infusion of BPX-501 cells is safe and well tolerated. The 100-day CI of skin-only grade I-II acute GvHD ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02065869

NCT02065869 | Safety Study of Gene Modified Donor T ... This is a Phase I/II study evaluating the safety and feasibility of BPX-501 T cells infused after partially mismatched, related, TCR alpha beta T cell depleted ...

7. ir.bellicum.com ir.bellicum.com/news-releases/news-release-details/bellicum-pharmaceuticals-announces-bpx-501-clinical-data-updates

Bellicum Pharmaceuticals Announces BPX-501 Clinical Data ... “These data also demonstrate high BPX-501 cell viability, expansion and persistence, and that the improvement of immune reconstitution is ...

8. onclive.com onclive.com/view/fda-puts-clinical-holds-on-trials-of-bpx501

FDA Puts Clinical Holds on Trials of BPX-501 The FDA has halted 4 US studies of BPX-501, a novel cellular immunotherapy for cancers and orphan inherited blood disorders, ...