TCRγδ T Cells + Blinatumomab for Blood Cancers

Overseen By Brandon Triplett, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: Active malignancy, Uncontrolled infection, Pregnancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for blood cancers that have returned or not responded to previous treatments. It focuses on using special T cells (a type of immune cell) and Blinatumomab (also known as Blincyto, a type of immunotherapy) to reduce complications after a transplant and improve recovery and survival. The trial seeks better ways to manage treatment side effects and prevent cancer recurrence. Participants with specific blood cancers like ALL or AML who have had a previous transplant might be suitable for this trial. As a Phase 2 trial, the research measures how well the treatment works in an initial, smaller group of people, offering participants a chance to contribute to advancements in cancer care.

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 using TCRγδ T cells in cancer treatments is generally safe. These cells, a small part of the immune system, can effectively attack cancer cells. Studies have found that they are safe when activated in patients and help fight tumors without major safety concerns.

Blinatumomab, another treatment under study, is already used for some blood cancers and has a known safety record. Real-world data indicate that serious side effects occur in about 12.5% of patients, suggesting it is generally well-tolerated. This treatment often helps patients achieve remission (no signs of cancer) with fewer side effects than some other treatments.

Overall, both TCRγδ T cells and Blinatumomab are considered safe based on existing research and have shown promising results in patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the TCRγδ T Cells + Blinatumomab treatment for blood cancers because it uses a unique combination of immunotherapy techniques. Unlike standard treatments such as chemotherapy or targeted therapies, this approach involves infusing specially prepared donor immune cells that have been tweaked to reduce the risk of rejection and enhance cancer-fighting capabilities. The use of Blinatumomab, a bi-specific T-cell engager, helps direct these immune cells to target cancer cells more effectively. This novel strategy could offer a more potent and personalized attack on cancer cells, potentially leading to better outcomes for patients with fewer side effects.

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

Research shows that using TCRγδ T cells with blinatumomab holds promise for treating blood cancers. Participants in this trial will receive a combination of treatments, including blinatumomab, which has significantly reduced treatment-related deaths and improved survival rates. One study showed that survival rates increased from 15.4% to 33.2% over three years. Additionally, blinatumomab has achieved an 80% complete response rate in patients with certain types of leukemia. Adding γδ T cells can enhance blinatumomab's effectiveness, as these cells boost the treatment's power. This combination aims to lower the risk of cancer returning and improve survival without causing severe side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Brandon Triplett, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for young people (≤21 years old) with certain blood cancers that didn't get better after a previous transplant. They need a family member who's at least a half-match as a donor, good heart and kidney function, not pregnant or breastfeeding, no other active cancers or uncontrolled infections, and able to perform some physical activities.

Inclusion Criteria

Left ventricular ejection fraction > 40%, or shortening fraction ≥ 25%.

My previous brain leukemia is treated and currently in remission.

My blood cancer returned or didn't respond after a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive a conditioning regimen of rabbit ATG, cyclophosphamide, fludarabine, thiotepa, melphalan, and rituximab prior to transplant

1-2 weeks

Transplantation

Infusion of TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cells, followed by G-CSF and blinatumomab

2 days

2 visits (in-person)

Engraftment Monitoring

Participants are monitored for engraftment by day +30 post-transplant

30 days

Follow-up

Participants are monitored for safety, effectiveness, and incidence of GVHD and relapse

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• TCRɑβ-depleted and CD45RA-depleted haploidentical donor progenitor cell transplantation

Trial Overview The study tests if T-cell depleted bone marrow transplants from half-matched family donors can help patients without using radiation. It also checks the safety of adding Blinatumomab post-transplant in CD19+ cancer cases to see if it improves survival rates and reduces complications like GVHD.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 13 Interventions

Participants receive a conditioning regimen of antithymocyte globulin (rabbit), cyclophosphamide, mesna, fludarabine, thiotepa, tacrolimus (first 5 participants enrolled), sirolimus (used beginning with 6th enrolled participant), melphalan, rituximab. This is followed by HPC,A infusion (transplant), then by G-CSF and blinatumomab. Cells for infusion are prepared using the CliniMACS System.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

In a study of 197 patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, blinatumomab demonstrated a significantly higher complete remission (CR) rate of 80.8% compared to 53.8% for conventional chemotherapy, indicating its greater efficacy.

Blinatumomab also led to a lower regimen-related mortality rate (1.9% vs. 40.4%) and improved overall survival at 3 years (33.2% vs. 15.4%), highlighting its safety and effectiveness as a treatment option before allogeneic hematopoietic cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior survival outcome of blinatumomab compared with conventional chemotherapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia: a propensity score-matched cohort analysis. Yoon, JH., Kwag, D., Lee, JH., et al.[2023]

Gamma delta (γδ) T cells are a promising option for cancer immunotherapy, particularly for hematologic malignancies, due to their unique properties that allow them to target tumors without major histocompatibility complex (MHC) restrictions.

Their ability to act like antigen-presenting cells and their ease of expansion from peripheral blood make γδ T cells a strong candidate for allogeneic adoptive cellular therapy, potentially improving treatment outcomes for patients with difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic gamma delta T cells as adoptive cellular therapy for hematologic malignancies. Jhita, N., Raikar, SS.[2022]

A systematic analysis of CAR T-cell therapy adverse events revealed 5,112 reports of hematotoxicity, highlighting significant under-reporting of severe conditions like hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC), which have high mortality rates of 69.9% and 59.6%, respectively.

The study identified 23 hematologic adverse events that were significantly over-reported compared to the general database, emphasizing the need for increased awareness and monitoring of these rare but potentially fatal toxicities in CAR T therapy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. Song, Z., Tu, D., Tang, G., et al.[2023]

Blinatumomab, a bispecific T-cell engager, has shown effectiveness in achieving negative minimal residual disease in patients with relapsed or refractory pre-B acute lymphoblastic leukemia after conventional chemotherapy.

In a case study, a patient with good health underwent successful allogenic stem cell transplantation after just one cycle of blinatumomab, suggesting its potential as an off-label treatment to enhance cytological remission before transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Blinatumomab as a bridge to trasplantation in refractory Philadelphia chromosome negative b-cell acute lymphoblastic leukemia: a case report]. Rodríguez-Ferreras, A., Zapico-García, I.[2019]

A new protocol was developed to effectively expand γδ T cells from healthy donors for use in treating patients with acute myeloid leukemia (AML), achieving over 229,000-fold expansion of these cells.

The expansion process involves activating γδ T cells with FDA-approved zoledronic acid and interleukin-2, followed by purification and further expansion using engineered artificial antigen-presenting cells, making it a promising approach for cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion and Enrichment of Gamma-Delta (γδ) T Cells from Apheresed Human Product. Landin, AM., Cox, C., Yu, B., et al.[2021]

Blinatumomab therapy before allogeneic hematopoietic cell transplantation (allo-HCT) in pediatric patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) effectively induced minimal residual disease (MRD)-negative remissions, leading to improved leukemia-free survival (LFS) compared to chemotherapy alone.

Importantly, blinatumomab did not increase the risk of post-transplant complications such as graft-versus-host disease (GVHD) or graft failure, suggesting it is a safe option for pre-HCT treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab Therapy Is Associated with Favorable Outcomes after Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients with B Cell Acute Lymphoblastic Leukemia. Llaurador, G., Shaver, K., Wu, M., et al.[2023]

In a study of 168 patients with refractory/relapsed B-cell acute lymphoblastic leukemia, those who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) after CAR-T therapy had similar long-term survival rates compared to those who underwent haplo-HSCT after achieving minimal residual disease-negative complete remission from chemotherapy.

Patients who achieved a first complete remission (CR1) after chemotherapy had better overall survival and leukemia-free survival rates than those who had a second or more complete remission (≥CR2), highlighting the importance of achieving an earlier remission for better transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparable outcomes in patients with B-cell acute lymphoblastic leukemia receiving haploidentical hematopoietic stem cell transplantation: Pretransplant minimal residual disease-negative complete remission following chimeric antigen receptor T-cell therapy versus chemotherapy. Yang, TT., Meng, Y., Kong, DL., et al.[2022]

Citations

1. withpower.com withpower.com/trial/phase-3-leukemia-myelomonocytic-juvenile-5-2016-69f61

TCRγδ T Cells + Blinatumomab for Blood Cancers Blinatumomab also led to a lower regimen-related mortality rate (1.9% vs. 40.4%) and improved overall survival at 3 years (33.2% vs. 15.4%), highlighting its ...

2. nature.com nature.com/articles/s41598-021-91784-1

The potential of adoptive transfer of γ9δ2 T cells to ... Our results suggest that the addition of γ9δ2 T cells to the blinatumomab treatment regimens could be an effective approach to enhancing blinatumomab's ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10024132/

Immunotherapeutic potential of blinatumomab-secreting ... γ9δ2 T cells can serve as effector cells for blinatumomab action. Effector memory γ9δ2 T cells survive for at least 7 days in vivo.

4. ashpublications.org ashpublications.org/blood/article/119/26/6226/105629/Immunopharmacologic-response-of-patients-with-B

Immunopharmacologic response of patients with B-lineage ... T cell–engaging CD19/CD3-bispecific BiTE Ab blinatumomab has shown an 80% complete molecular response rate and prolonged leukemia-free survival in patients.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10808317/

Gamma/delta T cells as cellular vehicles for anti-tumor immunity Furthermore, as engineered γδ T cells exhibit similar anti-tumor efficacy but generally secrete lower levels of cytokines compared with their ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32076826/

Safety and efficacy of blinatumomab: a real world data Median leukemia-free survival was 8.7 months, and median overall survival was 15.2 months. Median leukemia-free survival and overall survival ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5888/527632/Efficacy-and-Safety-Profile-of-Blinatumomab-in

Efficacy and Safety Profile of Blinatumomab in Relapsed ... Blinatumomab is an effective treatment for inducing remission in adults with relapsed or refractory BCP-ALL and has fewer side effects as compared to multi- ...

8. blincytohcp.com blincytohcp.com/clinical-data/adult-aya/real-world-evidence-study

Real-World Evidence in Adult & AYA B-cell ALL See real-world clinical outcomes for BLINCYTO® (blinatumomab) in treating adult and AYA patients with B-cell acute lymphoblastic leukemia (ALL).

9. sciencedirect.com sciencedirect.com/science/article/pii/S0145212625005880

Efficacy and safety of blinatumomab for CD19 + acute ... Blinatumomab has been safely given to patients excluded from clinical trials. •. Efficacy outcomes were similar to clinical trial cohorts by treatment setting.

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38662275/

Real-world evidence on treatment pattern, effectiveness ... Grade ≥ 3 adverse events were observed in 12.5% patients. Blinatumomab was found to be effective with a tolerable safety profile in real world setting. Keywords ...