Gene Modified T-cells + Stem Cell Transplant for Leukemia

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

36 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Gene Modified T-cells + Stem Cell Transplant for Leukemia?

Research shows that bone marrow transplantation (a type of stem cell transplant) can significantly improve outcomes for leukemia patients, especially when performed early in the disease. It has been shown to cure 50 to 60% of patients with certain types of leukemia when using a matched donor. ^{1 2 3 4 5}

What safety data exists for bone marrow transplantation in leukemia treatment?

Bone marrow transplantation (BMT) has been used to treat leukemia, but it carries risks such as graft-versus-host disease (GVHD), infections, and liver problems. While BMT can lead to long remissions and possible cures, about 20% of patients may die from therapy-related complications, and the risk of relapse remains. Safety measures, like using cyclosporin-A to prevent GVHD, have improved outcomes. ^{1 6 7 8 9}

What makes the Gene Modified T-cells + Stem Cell Transplant treatment unique for leukemia?

This treatment is unique because it combines gene-modified T-cells, which are engineered to target specific cancer antigens, with a stem cell transplant to enhance the immune response against leukemia. This approach aims to improve the effectiveness of the immune system in fighting cancer compared to traditional chemotherapy or transplantation alone. ^{10 11 12 13 14}

What is the purpose of this trial?

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 relative. The research study will test whether immune cells, called T cells, which come from the donor relative and are specially grown in the laboratory and then given back to the patient along with the stem cell transplant (T cell addback), can help the immune system recover faster after the transplant. As a safety measure, these T cells have been "programmed" with a "self-destruct switch" so that if, after they have been given to the patient, the T cells start to react against the tissues (called "graft versus host" disease, GVHD), the T cells can be destroyed.

Research Team

Bellicum Pharmaceuticals

Principal Investigator

Bellicum Pharmaceuticals, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Indications, technique and risks in bone marrow transplantation in adulthood]. [2008]

2. France pubmed.ncbi.nlm.nih.gov

Indications for bone marrow grafting. [2009]

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

Results of allogeneic bone marrow transplantation for acute leukemia have improved in Europe with time--a report of the acute leukemia working party of the European group for blood and marrow transplantation (EBMT). [2007]

4. China pubmed.ncbi.nlm.nih.gov

[Preliminary study of HLA haplotype matched and T-cell undepleted allogeneic bone marrow transplantation for treatment of leukemia]. [2006]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[Bone marrow transplantation in leukemia: possibilities and problems]. [2013]

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

Current status of bone marrow transplantation in pediatric oncology. [2019]

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

Bone marrow transplantation: a review. [2018]

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

[New development in clinical bone marrow transplantation in leukemia]. [2013]

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

Bone marrow transplantation in leukemia. Current status. [2019]

10. United States 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. [2021]

11. Brazil pubmed.ncbi.nlm.nih.gov

Immunotherapy with natural killer cells: a possible approach for the treatment of Acute Myeloid Leukemia also in Brazil. [2017]

12. Japan pubmed.ncbi.nlm.nih.gov

Adoptive immunotherapy utilizing cancer antigen-specific T-cell receptors. [2017]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Treatment with Living Drugs: Pharmaceutical Aspects of CAR T Cells. [2022]

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

Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells. [2018]