Stem Cell Transplant with T-allo10 Addback for Blood Diseases

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Porteus, Matthew, MD

Disqualifiers: Pregnancy, Investigational agents, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called T-allo10 to determine if it can safely rebuild the immune system after an Allogeneic Stem Cell Transplant. It targets individuals with serious blood diseases who have undergone a transplant that removes certain immune cells to prevent complications. T-allo10 aims to enhance the immune system without causing severe side effects like Graft-versus-Host Disease, where donor cells attack the recipient's body. Individuals with life-threatening blood cancers, such as high-risk leukemia, who have already received the specific stem cell transplant, may be suitable for this study. As a Phase 1 trial, this research seeks to understand how T-allo10 functions in people, offering participants the chance to be among the first to receive this innovative treatment.

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?

A previous study showed that T-allo10 infusion had promising safety results. The research found that this treatment not only helped the immune system recover faster but also reduced the risk of severe Graft-versus-Host Disease (GvHD), a condition where donor cells attack the recipient's body. In young patients, T-allo10 also appeared to lower the number of viral infections compared to past cases.

Since this trial is in its early stages, the main goal is to find the right dose that is both safe and effective. Although not everything is known about its safety, early data suggests that T-allo10 is generally well-tolerated. As a Phase 1 trial, the primary focus is to ensure the treatment is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this treatment because it uses T-allo10 cells to enhance the effectiveness of allogeneic stem cell transplants for blood diseases. Unlike traditional stem cell transplants that rely solely on donor cells, this approach adds back T-allo10 cells to boost the immune response and potentially improve engraftment and recovery. The unique aspect lies in the dose manipulation of T-allo10 cells, which is being tested across different levels to optimize patient outcomes. This innovative technique could offer a more personalized and potentially more effective approach to treating blood diseases compared to existing methods.

What evidence suggests that T-allo10 cell therapy might be an effective treatment for blood diseases?

Research has shown that T-allo10 cell infusion can significantly aid in rebuilding the immune system in individuals with blood cancers. In this trial, participants will receive an alpha-beta depleted stem cell transplant followed by a T-allo10 cell addback at varying dose levels. Studies have found that T-allo10 reduces the risk of severe Graft-versus-Host Disease (GvHD), a common issue after stem cell transplants. It also aims to lower the chances of infections and cancer recurrence. Early results suggest that T-allo10 is safe and supports immune recovery in children and young adults. Overall, T-allo10 appears promising in enhancing the safety and effectiveness of stem cell transplants for treating blood diseases. ^{2 3 4 6 7}

Who Is on the Research Team?

Alice Bertaina, MD, PhD

Principal Investigator

Associate Professor of Pediatrics, Stem Cell Transplantation

Are You a Good Fit for This Trial?

This trial is for children and adults aged over 1 month and under 45 years with life-threatening blood diseases, who've had a specific type of stem cell transplant (αβdepleted-HSCT) and are part of another study (NCT04249830). They must not have severe Graft-versus-Host Disease or be pregnant. Participants need to give consent personally or through a legal representative.

Inclusion Criteria

I am between 1 month and 45 years old and weigh at least 10 Kg.

Patients deemed eligible for allogeneic HSCT under the originating study, NCT 04249830

I have had a stem cell transplant and my bone marrow is making blood cells.

Exclusion Criteria

Not eligible to receive HSCT on NCT04249830

I or my donor cannot undergo an extra cell collection procedure before donating cells for the study.

You have taken part in another research study within the past month.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo αβ-depleted HSCT followed by T-allo10 cell infusion to determine the recommended Phase 2 dose (RP2D) and evaluate safety and efficacy

8 weeks

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for immune reconstitution and leukemia-free survival

60 days

Regular visits for monitoring immune reconstitution

Long-term follow-up

Participants are assessed for leukemia-free survival and disease relapse

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Allogeneic Stem Cell Transplant
• CliniMACS Prodigy System
• T-allo10 cells addback

Trial Overview The trial tests the safety of T-allo10 cells after an αβdepleted-HSCT in patients with hematologic malignancies. It aims to find the right dose that boosts immune recovery while minimizing severe GvHD risk. The study includes two phases: determining the optimal dose and then assessing its safety and effectiveness.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 3 Interventions

The participant will undergo a alpha-beta depleted stem cell transplant using donor cells. The participant's cells will then be manipulated via a T-allo10 cell addback to reach a dose level of 1 X 10\^6/kg

Group II: Cohort 2 Experimental Treatment 3 Interventions

The participant will undergo a alpha-beta depleted stem cell transplant using donor cells. The participant's cells will then be manipulated via a T-allo10 cell addback to reach a dose level of 3 X 10\^5/kg

Group III: Cohort 1 Experimental Treatment 3 Interventions

The participant will undergo a alpha-beta depleted stem cell transplant using donor cells. The participant's cells will then be manipulated via a T-allo10 cell addback to reach a dose level of 1 X 10\^5/kg

Allogeneic Stem Cell Transplant is already approved in United States, European Union for the following indications:

Approved in United States as Allogeneic Hematopoietic Stem Cell Transplantation for:

• Acute Leukemia
• Chronic Leukemia
• Lymphoma
• Multiple Myeloma
• Other hematologic malignancies

Approved in European Union as Allo-HSCT for:

• Acute Leukemia
• Chronic Leukemia
• Lymphoma
• Multiple Myeloma
• Other hematologic malignancies

Who Is Running the Clinical Trial?

Porteus, Matthew, MD

Lead Sponsor

Trials

2

Recruited

30+

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Roncarolo, Maria Grazia, MD

Lead Sponsor

Trials

2

Recruited

30+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

Published Research Related to This Trial

Allogeneic haematopoietic stem-cell transplantation (SCT) is an effective curative treatment for blood-related diseases, but it can lead to graft-versus-host disease (GVHD) due to donor T cells attacking the recipient's tissues.

Research using mouse models is being conducted to find ways to reduce GVHD while still allowing donor T cells to effectively fight off cancer cells, which is crucial for maximizing the benefits of SCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Graft-versus-host disease. Shlomchik, WD.[2021]

In a study of 65 pediatric patients with β-thalassaemia major (TM) and sickle cell disease (SCD) who underwent allogeneic hematopoietic stem cell transplant (allo-HSCT), the three-year event-free survival rate was 81% for TM and 79% for SCD, indicating a high success rate for this curative treatment.

Overall survival rates were also promising, with 92% for TM and 85% for SCD, suggesting that allo-HSCT is an effective option for treating severe hemoglobinopathies in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell transplantation in pediatric patients with thalassemia and sickle cell disease: An experience of the Spanish Working Group for Bone Marrow Transplantation in Children (GETMON). Alonso, L., González-Vicent, M., Belendez, C., et al.[2020]

In a pilot study involving 10 patients aged 45 and older with hematologic malignancies, CD34+ peripheral blood stem cell transplantation (CD34+-PBSCT) led to prompt engraftment and an acceptable level of transplant-related morbidity and mortality, despite some patients developing graft-versus-host disease (GVHD).

The study suggests that delaying T-cell add-back (TCAB) after CD34+-PBSCT may help restore the graft-versus-tumor effect while minimizing early transplant-related complications, indicating a potential strategy for improving outcomes in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic peripheral blood stem cell transplantation with CD34+-cell selection and delayed T-cell add-back in adults. Results of a single center pilot study. Martino, R., Martín-Henao, G., Sureda, A., et al.[2006]

A unique population of CD19+/CD3+ T cells was identified in a patient undergoing CAR T-cell therapy after receiving haploidentical HSCT, suggesting that these cells originated from a previous treatment with a genetically modified T-cell product (RivoCel).

The presence of these CD19-expressing T cells may complicate CAR T-cell therapy, as they were eliminated during the CAR transduction process, indicating that using alternative markers instead of CD19 for tracking post-transplant T cells could be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of dual positive CD19+/CD3+ T cells in a leukapheresis product undergoing CAR transduction: a case report. Schultz, L., Patel, S., Davis, KL., et al.[2021]

Allogeneic stem cell transplantation (allo-SCT) is a powerful treatment for hematologic malignancies, leveraging both intensive chemoradiotherapy and the immune response from donor cells to potentially cure diseases, though challenges like disease relapse and graft-versus-host disease remain significant.

The introduction of CAR-T cell therapy has transformed the treatment landscape for certain blood cancers, particularly acute lymphoblastic leukemia and specific lymphomas, indicating a shift in treatment paradigms and expanding options beyond traditional allo-SCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms? Martino, M., Canale, FA., Naso, V., et al.[2023]

In a study involving 12 patients with high-risk hematologic malignancies, T-cell depleted haploidentical-HSCT combined with IL-10-pretreated donor T cells led to rapid immune reconstitution in five patients, with four achieving complete disease remission and remaining free of immunosuppression for over 7 years.

The use of IL-10-anergized donor T cells helped limit graft-versus-host disease (GvHD) while promoting tolerance, suggesting that Tr1 cell-based therapy could be a promising approach for treating malignancies and immune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological Outcome in Haploidentical-HSC Transplanted Patients Treated with IL-10-Anergized Donor T Cells. Bacchetta, R., Lucarelli, B., Sartirana, C., et al.[2022]

Cell therapy began in 1968 with the first successful transplantation of hematopoietic stem cells, which has since helped thousands of patients with immune disorders like Wiskott-Aldrich syndrome and Severe Combined ImmunoDeficiency (SCID).

Despite its success, the effectiveness of hematopoietic stem cell therapy is still limited by immunologic challenges related to HLA compatibility, which poses significant obstacles for broader application in treating various diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cell therapy for inherited diseases of the hematopoietic system]. Cavazzana-Calvo, M., Dal-Cortivo, L., André-Schmutz, I., et al.[2007]

The study developed a specialized cell product called T-allo10, enriched with Type 1 regulatory T (Tr1) cells, which can effectively suppress graft-versus-host disease (GvHD) in patients undergoing HLA-mismatched hematopoietic stem cell transplantation (allo-HSCT).

Tr1 cells showed a unique mechanism of action involving specific surface proteins (CTLA-4 and PD-1) that are crucial for their suppressive function, and these cells were found to persist in patients' blood for up to a year after treatment, indicating their potential for long-term therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alloantigen-specific type 1 regulatory T cells suppress through CTLA-4 and PD-1 pathways and persist long-term in patients. Chen, PP., Cepika, AM., Agarwal-Hashmi, R., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03198234

Study Details | Use of T-allo10 in Hematopoietic Stem Cell ... T-allo10 cell infusion is being developed to prevent acute Graft-versus-Host Disease (GvHD) and induce graft tolerance in patients with hematologic malignancies ...

2. astctjournal.org astctjournal.org/article/S2666-6367(23)01771-2/fulltext

Enhanced Immune Reconstitution and Reduced GvHD ... T-allo10 infusion aims to enhance IR, reduce the risks of infections and leukemic relapse, without severe GvHD.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124062773

T-allo10 Immunotherapy Results in Enhanced Early ... In conclusion, Phase I trial results show that T-allo10 infusion is safe and significantly improves early IR and reduces GvHD risk in pediatric and young adult ...

4. onclive.com onclive.com/view/dr-bertaina-on-t-allo10-infusion-in-young-patients-with-hematologic-malignancies

Dr Bertaina on T-allo10 Infusion in Young Patients With ... Overall, the phase 1 results of this clinical trial demonstrate the efficacy of T-allo10 infusion in enhancing immune reconstitution and ...

5. withpower.com withpower.com/trial/phase-1-hematologic-diseases-2020-a4257

Stem Cell Transplant with T-allo10 Addback for Blood ... Research shows that adding T-cells back after stem cell transplants can help restore the body's ability to fight tumors while reducing early death risks.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04640987

NCT04640987 | Stem Cell Transplant From Donors After ... The purpose of this study is to determine the safety of a cell therapy, T-allo10, after αβdepleted-HSCT in the hopes that it will boost the adaptive immune ...

7. stanfordhealthcare.org stanfordhealthcare.org/trials/u/NCT03198234.html

Use of T-allo10 in Hematopoietic Stem Cell ... The purpose of this phase 1 study is to determine the safety and tolerability of a cell therapy, T-allo10, to prevent GvHD in patients receiving mismatched ...