Gene Modified T-cells + Stem Cell Transplant for Leukemia

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bellicum Pharmaceuticals

Disqualifiers: Pregnancy, HIV, Myelofibrosis, 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 new treatment for individuals with certain blood cancers undergoing a stem cell transplant from a partially matched donor. The goal is to determine if adding specially modified immune cells (T cells) from the donor can enhance the recovery of patients' immune systems after the transplant. These T cells include a "self-destruct switch" to prevent unwanted reactions against the patient's body. Candidates for this trial have blood cancers like leukemia or lymphoma and lack a fully matched stem cell donor. As a Phase 1 trial, this research aims to understand how the treatment functions in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

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, when used with a stem cell transplant, are generally safe and well tolerated. In earlier studies, patients who received BPX-501 cells experienced positive safety outcomes, with most side effects being mild and manageable. A key feature of this treatment is a built-in "self-destruct switch." If the BPX-501 cells cause issues like graft versus host disease (GVHD), these cells can be quickly deactivated to control any negative effects.

For the Rimiducid used in this trial, studies have shown it helps manage potential side effects by activating this safety switch. Patients who received Rimiducid experienced fewer severe complications because the switch helps prevent serious reactions.

Overall, past studies suggest that both BPX-501 cells and Rimiducid enhance the treatment's safety for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the BPX-501 treatment because it uses gene-modified T-cells to enhance the effects of a stem cell transplant for leukemia patients. Unlike standard treatments like chemotherapy or radiation, which can be harsh and non-specific, BPX-501 is designed to selectively boost the immune system by infusing specially engineered T-cells. This approach not only targets leukemia cells more precisely but also includes the use of Rimiducid, a dimerizer drug, which can be administered if patients experience graft-versus-host disease (GVHD) that does not respond to standard therapies. This combination of targeted immune enhancement and a backup plan for managing GVHD makes BPX-501 a promising advancement in leukemia treatment.

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

Research has shown that BPX-501, a type of specially modified immune cell, holds promise for treating blood cell cancers. In this trial, participants will receive varying doses of BPX-501 following a stem cell transplant. Studies have found that BPX-501 can safely aid immune system recovery after a stem cell transplant. Earlier research indicated that only about 11.83% of patients experienced moderate cases of graft-versus-host disease (GVHD), with severe cases being even rarer. The treatment includes a safety feature—a "self-destruct switch"—to manage GVHD if it occurs. Another component, Rimiducid, is administered if needed and has effectively reversed GVHD quickly. Overall, these treatments offer a hopeful approach to managing complications after a transplant. ^{5 6 7 8 9}

Who Is on the Research Team?

Bellicum Pharmaceuticals

Principal Investigator

Bellicum Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

Adults aged 18-65 with certain blood cancers like leukemia or lymphoma, who lack a fully matched stem cell donor and are eligible for a transplant. Participants must have at least a half-matched (4/8) donor available, good organ function, and specific types of cancer in remission or high-risk states.

Inclusion Criteria

I am eligible for a stem cell transplant from a donor.

I don't have a matching donor or my disease is worsening too quickly.

My donor and I share at least one genetic match in specific areas.

Exclusion Criteria

Bovine product allergy

I had a stem cell transplant using my own cells less than 3 months ago.

I am HIV positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BPX-501 T cells after a partially mismatched, related, T cell-depleted HSCT. Rimiducid may be administered if GvHD occurs.

24 months

Follow-up

Participants are monitored for safety, immune reconstitution, and incidence of GvHD and relapse.

24 months

What Are the Treatments Tested in This Trial?

Interventions

• BPX-501
• Rimiducid
• Stem Cell Transplant

Trial Overview The trial is testing genetically modified T-cells from partially matched donors after stem cell transplants to see if they can help the immune system recover faster. These T-cells have a 'self-destruct switch' to prevent them from attacking the patient's body.

How Is the Trial Designed?

Group I: SCT, BPX-501 dose 4, Rimiducid if needed Experimental Treatment 3 Interventions

3x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant . Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.

Group II: SCT, BPX-501 dose 3, Rimiducid if needed Experimental Treatment 3 Interventions

1x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.

Group III: SCT, BPX-501 dose 2, Rimiducid if needed Experimental Treatment 3 Interventions

5x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.

Group IV: SCT, BPX-501 dose 1, Rimiducid if needed Experimental Treatment 3 Interventions

2x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant. Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.

Who Is Running the Clinical Trial?

Bellicum Pharmaceuticals

Lead Sponsor

Trials

28

Recruited

1,400+

Published Research Related to This Trial

Genetically engineered T cells targeting the CD33 antigen showed promising in vitro bispecificity and did not harm normal blood cell progenitors, suggesting a safer approach for treating acute myeloid leukemia (AML).

In vivo studies in mice demonstrated that these CAR-modified T cells effectively localized to tumor sites and exhibited antitumor activity, indicating potential for enhanced treatment outcomes in AML patients compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro and In Vivo Antitumor Effect of Anti-CD33 Chimeric Receptor-Expressing EBV-CTL against CD33 Acute Myeloid Leukemia. Dutour, A., Marin, V., Pizzitola, I., et al.[2021]

The article discusses a clinical trial for a new adoptive immunotherapy using gene-modified T cells that target the Wilms Tumor 1 (WT1) antigen, showing promise for treating refractory acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).

While this innovative approach has demonstrated clear and lasting clinical efficacy against tumors, it also poses risks of serious treatment-related adverse events, highlighting the need for careful management in developing powerful gene-modified T cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy utilizing cancer antigen-specific T-cell receptors. Tanimoto, K., Fujiwara, H.[2017]

All 15 leukemia patients who received allogeneic bone marrow transplantation (Allo-BMT) from HLA haplotype matched related donors successfully established engraftment, with median recovery times for granulocytes and platelets of 19 and 21 days, respectively.

While 33.3% of patients experienced acute graft-versus-host disease (GVHD), the combination of G-CSF stimulation for donors and a comprehensive GVHD prophylaxis program showed promise in managing complications, with 9 out of 15 patients remaining disease-free after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Preliminary study of HLA haplotype matched and T-cell undepleted allogeneic bone marrow transplantation for treatment of leukemia]. Ji, S., Chen, H., Wang, H.[2006]

Chimeric antigen receptor-modified T cells (CAR-Ts) are a promising new treatment for hematological malignancies, showing powerful efficacy against tumor cells by targeting specific cancer-associated antigens.

The review discusses the CAR-T manufacturing process and highlights ongoing clinical trials for various blood cancers, including acute lymphoblastic leukemia and multiple myeloma, indicating a growing interest and development in this area of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells. Allegra, A., Innao, V., Gerace, D., et al.[2018]

Citations

1. 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 ...

2. 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 ... Acute GvHD Grade 2-4 was 11.83%; acute GvHD Grade 3-4 was 4.70%; Chronic GvHD Grade Moderate-Severe was 3.23%; Non-relapse mortality (NRM) of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03699475?term=AREA%5BExpandedAccessNCTId%5DNCT03639844&rank=1

NCT03699475 | Study of Haplo-HSCT + Rivogenlecleucel ... This study compares the safety and effectiveness of giving rivogenlecleucel (BPX-501 T cells) to patients with AML or MDS post haploidentical hematopoietic ...

4. ashpublications.org ashpublications.org/blood/article/126/23/1931/105323/Clinical-Outcome-after-Adoptive-Infusion-of-BPX

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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6646494/

Summary of the Highlights of 2019 ASTCT Meeting by ... BPX-501 T cells provide broad virus and tumor specific immunity; the safety switch can promptly resolve GVHD following administration of rimiducid, which leads ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01744223

Safety Study of Gene Modified Donor T-cells Following ... This study will evaluate patients with blood cell cancers who are going to have an allogeneic (donor) blood stem cell transplant from a partially matched ...

7. 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 ...

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03699475/

Clinical Trial: NCT03699475 This study compares the safety and effectiveness of giving rivogenlecleucel (BPX-501 T cells) to patients with AML or MDS post haploidentical ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10336773/

BPX-501 T-cells interfere with minimal residual disease ... Here we present an unusual complication of BPX-501 cells affecting the clinical workflow and emphasizing the need for good communication between ...