Allogeneic T Cell Therapy for Blood Cancers

Overseen By Frédéric LEHMANN, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Smart Immune SAS

Disqualifiers: Cord blood, Prior allogeneic transplant, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 100 days

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment called SMART101, an allogeneic T cell therapy, for individuals with blood cancers. It specifically examines how well this treatment can help rebuild the immune system after a special type of stem cell transplant. The trial includes two groups: one for adults with certain types of leukemia or myelodysplastic syndrome, and another for children with specific types of leukemia. Adults and children with these conditions who are set to undergo a specific stem cell transplant may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new 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. However, it mentions that you should not have had treatment with another cellular therapy within one month before joining the trial.

Is there any evidence suggesting that SMART101 is likely to be safe for humans?

Research shows that SMART101, a type of T-cell therapy, aims to rebuild the immune system after a stem cell transplant in people with blood cancers. In earlier studies, researchers tested SMART101 to assess its safety for both adults and children.

These studies indicate that SMART101 is generally well-tolerated, with most people not experiencing severe reactions. Some side effects, such as fever or chills, have been reported, but they are usually mild and common after any cell therapy.

Since this trial is in the early stages, researchers continue to learn about the safety and effectiveness of SMART101. Early trials typically include more safety checks to ensure participants' well-being.

Overall, the results so far are promising, but more research is needed to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for blood cancers?

Researchers are excited about SMART101 because it offers a novel approach to treating blood cancers like acute leukemia and myelodysplastic syndrome. Unlike standard treatments that may involve chemotherapy or autologous stem cell transplants, SMART101 utilizes allogeneic T cell therapy, which involves using immune cells from a healthy donor to target and destroy cancer cells. This method has the potential to enhance the body's natural immune response against cancer more effectively. Additionally, SMART101 is specifically designed to be T cell depleted, which may reduce the risk of complications such as graft-versus-host disease, a common issue with traditional transplants.

What evidence suggests that SMART101 might be an effective treatment for blood cancers?

Research has shown that SMART101, a type of cell therapy, might help rebuild the immune system after a stem cell transplant for blood cancers. Early results suggest it is generally safe, with most patients not experiencing severe side effects. In this trial, SMART101 will be used for both adult and pediatric patients with hematological malignancies. SMART101 works by using special cells from a donor to jumpstart the patient's immune system. A strong immune system is crucial for fighting off infections and possibly cancer cells. Overall, the treatment appears promising for aiding recovery in both adults and children after a transplant. ^{1 2 4 6 7}

Who Is on the Research Team?

Jaap-Jan Boelens, MD, PhD

Principal Investigator

Memorial Sloan Kettering Cancer Center (MSKCC)

Are You a Good Fit for This Trial?

This trial is for children and adults with blood cancers who need a stem cell transplant but don't have a perfect donor match. They should be in at least their second complete remission or have low levels of remaining cancer cells. Participants must be fit enough for the transplant, with good organ function and performance status.

Inclusion Criteria

Group A (adults): Adult patients affected by Acute Myeloid Leukemia (AML) with high risk in CR1, chemo-refractory relapse, or ≥ CR2; Acute Lymphoblastic Leukemia (ALL) with chemo-refractory relapse, high risk in CR1, or ≥ CR2; Acute leukemia of ambiguous lineage with ≥ CR1 and MRD <5%; Myelodysplastic Syndrome (MDS) meeting specific criteria; Patient eligible for a T-depleted allogeneic HSCT; Age ≥ 18y with Karnofsky index ≥ 70% and normal organ function. Group B (pediatrics): Pediatric patients affected by AML with high risk in CR1, chemo-refractory relapse, or ≥ CR2; ALL with chemo-refractory relapse, high risk in CR1, or ≥ CR2; Acute leukemia of ambiguous lineage with ≥ CR1 and MRD <5%; Patient eligible for a T-depleted allogeneic HSCT; Age < 18y without a matched sibling donor; Lansky ≥ 70% / Karnofsky performance status ≥ 70% and normal organ function.

Exclusion Criteria

Use of an HLA matched Cord Blood (8/8 allele matched) or haploidentical donor; Prior therapy with allogeneic stem cell transplantation; Treatment with another cellular therapy within one month before inclusion.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SMART101 injection to accelerate immune reconstitution after T cell depleted allogeneic HSCT

100 days

Regular visits for monitoring adverse events and T cell counts

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on T cell immune reconstitution

up to 12 months

Periodic visits for immune monitoring

What Are the Treatments Tested in This Trial?

Interventions

• SMART101

Trial Overview The study tests SMART101 injections to speed up immune recovery after a T-cell depleted stem cell transplant in patients with blood cancers. It aims to determine how safe and effective these cultured human T lymphoid progenitors are post-transplant.

How Is the Trial Designed?

Group I: Pediatric patients affected by hematological malignancies Experimental Treatment 1 Intervention

Pediatric patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) eligible for a T depleted allogeneic HSCT

Group II: Adult patients affected by hematological malignancies Experimental Treatment 1 Intervention

Adult patients affected by acute leukemia (AML, ALL or acute leukemia of ambiguous lineage) or myelodysplastic syndrome eligible for a T depleted allogeneic HSCT

Who Is Running the Clinical Trial?

Smart Immune SAS

Lead Sponsor

Trials

3

Recruited

90+

Published Research Related to This Trial

In a pilot study involving 11 patients with adult T-cell leukaemia/lymphoma, allogeneic haematopoietic stem-cell transplantation (allo-HSCT) showed promising results, with a 1-year overall survival rate of 53% and a disease-free survival rate of 45%.

All 10 patients who survived more than 30 days after the transplant achieved complete remission, indicating that allo-HSCT can be an effective treatment option for ATL, although some patients experienced complications like graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic haematopoietic stem cell transplantation for the treatment of adult T-cell leukaemia/lymphoma. Kami, M., Hamaki, T., Miyakoshi, S., et al.[2019]

Allogeneic hematopoietic stem cell transplantation (HCT) is the standard treatment for high-risk acute leukemias, but many patients still face relapse, highlighting the need for new therapies.

Adoptive T-cell immunotherapy shows promise as a post-HCT treatment option, leveraging advancements in T-cell therapy to address challenges in preventing disease recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation of anti-tumor immunity by adoptive T-cell transfer after allogeneic hematopoietic stem cell transplantation. Bleakley, M., Turtle, CJ., Riddell, SR.[2023]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed on 10 patients with T cell Lymphoblastic lymphoma (T-LBL), resulting in a 70% overall survival rate and a 70% disease-free survival rate after a median follow-up of 26 months.

Despite the promising survival outcomes, T-LBL patients experienced a high relapse rate of 10%, and complications such as acute graft versus host disease (GVHD) occurred in 5 patients, highlighting the need for careful monitoring post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allogeneic Hematopoietic Stem Cell Transplantation for Treatment of T Cell Lymphoblastic Lymphoma - Clinical observation of 10 Cases]. Gong, F., Chen, H., Zhao, LY., et al.[2018]

In a study of 25 patients undergoing HLA-identical bone marrow transplantation, higher frequencies of anti-recipient helper T-lymphocyte precursors (HTLp) in donor blood were linked to a greater incidence of moderate-to-severe acute graft-versus-host disease (GVHD).

The HTLp assay can effectively identify significant differences in minor histocompatibility antigens between donors and recipients, suggesting it could be useful for selecting optimal donor matches and determining the need for enhanced GVHD prevention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequency of anti-recipient alloreactive helper T-cell precursors in donor blood and graft-versus-host disease after HLA-identical sibling bone-marrow transplantation. Schwarer, AP., Jiang, YZ., Brookes, PA., et al.[2019]

Allogeneic hematopoietic stem cell transplantation (allo-HCT) without posttransplantation cyclophosphamide (PTCY) shows a 1-year overall survival rate of 34.5% and a 5-year rate of 17.7% in patients with adult T-cell leukemia-lymphoma (ATL), based on a retrospective study of 46 patients.

Despite these survival rates, the study highlights a concerningly high non-ATL mortality rate of 41.3% at 1 year and 55.8% at 5 years, indicating significant risks associated with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective analysis of haplo-identical HLA-mismatch hematopoietic transplantation without posttransplantation cyclophosphamide for GVHD prophylaxis in patients with adult T-cell leukemia-lymphoma. Yoshimitsu, M., Utsunomiya, A., Fuji, S., et al.[2020]

A study updating the risk assessment for using HTLV-1-seropositive donors in allogeneic hematopoietic stem cell transplantation (allo-HCT) for aggressive adult T cell leukemia-lymphoma (ATL) found no significant difference in overall survival or mortality rates compared to HTLV-1-negative donors, suggesting that these donors may be safe to use if no alternatives are available.

The analysis included a larger number of HTLV-1-seropositive donors and longer observation periods, reinforcing the idea that the previous concerns about increased ATL-related mortality with these donors may not be justified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation for ATL with HTLV-1 Antibody-Positive Donors. Yoshimitsu, M., Fuji, S., Utsunomiya, A., et al.[2021]

CD19, CD20 chimeric antigen receptor T (CAR T) cell therapy has shown an impressive complete response rate of over 80% in treating acute lymphoblastic leukemia, indicating its high efficacy for this type of cancer.

In a review of 72 patients who received donor-derived CAR T cells, only 6.9% developed graft versus host disease, suggesting that this therapy has a low risk of this serious side effect while effectively preventing relapse and clearing minimal residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor origin CAR T cells: graft versus malignancy effect without GVHD, a systematic review. Anwer, F., Shaukat, AA., Zahid, U., et al.[2022]

This study demonstrates that it is feasible to generate tumor antigen-specific T-cells from hematopoietic stem and progenitor cells (HSPC) sourced from adult healthy donors and AML patients, providing a potential new avenue for personalized T-cell immunotherapy.

Using HSPC avoids the risk of graft-versus-host disease associated with traditional T-cell receptor (TCR) therapy, as these cells do not express endogenous TCRs, although the maturation process is slower and yields are lower compared to cord blood HSPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells with a single tumor antigen-specific T-cell receptor can be generated in vitro from clinically relevant stem cell sources. Bonte, S., De Munter, S., Goetgeluk, G., et al.[2022]

In a study of 27 recipients of HLA6/6-matched haploidentical hematopoietic stem cell transplants, the efficacy and safety were found to be comparable to HLA3/6-matched transplants, with no significant differences in hematopoietic recovery or acute graft versus host disease incidence.

The 3-year disease-free survival and overall survival rates were similar between the two groups, indicating that the degree of HLA mismatch does not significantly impact outcomes in T-cell-replete haplo-HSCT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy between HLA6/6- and HLA3/6-matched haploidentical hematopoietic stem cell transplant in T-cell-replete transplants between parents and children. Yu, W., Wang, Y., Wu, D., et al.[2019]

The study successfully generated leukemia-reactive donor T cells from peripheral blood mononuclear cells, showing that this method can produce cells that specifically target leukemia while sparing non-leukemic cells, which is crucial for reducing the risk of graft-versus-host disease.

In 5 out of 6 donors, the generated T cells demonstrated significant anti-leukemic reactivity, primarily mediated by CD4+ T cells, indicating a promising approach for enhancing post-transplant immunotherapy in patients with acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic HLA-matched donor dendritic cells loaded with patient leukemic blasts preferentially induce CD4-positive leukemia-reactive donor lymphocytes. Thomas-Kaskel, AK., Portugal, TG., Herchenbach, D., et al.[2018]

In a review of 60 studies involving 913 participants, CAR-T cell therapy showed a promising complete response rate of 54.4% in patients with CD19+ hematologic malignancies, indicating its efficacy in treating certain blood cancers.

However, safety concerns were significant, with 55.3% of hematologic patients experiencing cytokine release syndrome and 37.2% experiencing neurotoxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis. Grigor, EJM., Fergusson, D., Kekre, N., et al.[2020]

Recent advancements in T-lymphocyte based therapies, particularly through donor lymphocyte infusion and ex vivo expansion of antigen-specific cytotoxic T lymphocytes, have shown promising sustained antitumor effects in patients with virus-associated lymphomas, such as those related to Epstein-Barr virus.

The development of robust gene transfer methodologies to human T lymphocytes is rapidly evolving, providing new opportunities for enhancing the efficacy and specificity of T-cell based therapies in treating hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic modification of human T lymphocytes for the treatment of hematologic malignancies. Hoyos, V., Savoldo, B., Dotti, G.[2021]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can lead to long survival in 30-40% of adult T-cell leukemia-lymphoma (ATL) patients, with no significant difference in survival rates between myeloablative and reduced intensity conditioning methods for patients aged 50-70.

Mild acute graft-versus-host disease is linked to better overall survival, and the cessation of immunosuppressants can trigger another remission in relapsed ATL patients, highlighting the potential of a graft-versus-ATL effect driven by activated T-cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma. Utsunomiya, A.[2017]

The study assessed the frequency of helper T lymphocyte precursors (HTLp) in 28 HLA-identical sibling pairs undergoing allogeneic PBSC transplantation, but found that HTLp frequency did not predict outcomes such as acute or chronic GVHD, transplant-related mortality, relapse, or overall survival.

Despite the HTLp assay showing potential in predicting risks for severe acute GVHD in other contexts, it was not effective in predicting outcomes for patients receiving HLA-identical donor stem cell transplants, suggesting its limited utility in this specific setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The helper T lymphocyte precursor (HTLp) frequency does not predict outcome after HLA-identical sibling donor G-CSF-mobilised peripheral blood stem cell transplantation. Healey, G., Schwarer, AP.[2004]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04959903

Safety and Efficacy of SMART101 in Pediatric and Adult ... The purpose of this study is to evaluate the safety and the efficacy of SMART101 (Human T Lymphoid Progenitor (HTLP)) injection to accelerate immune ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10430578/

P1403: SI101-01 PHASE I/II STUDY EVALUATING ... SMART101 is a cellular therapy using CD34-CD7+ T-lymphoid progenitors produced in culture from mobilized peripheral blood CD34+ cells of the transplant donor.

3. smart-immune.com smart-immune.com/articles/smart-immune-doses-first-leukemia-patients-with-protcell-therapy-smart101-in-reset-02-phase-i-ii-trial

Smart Immune Doses First Leukemia Patients with ProTcell ... Early data show that SMART101 is being well tolerated and has a safety profile in line with that observed in patients enrolled in the ongoing ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05768035

NCT05768035 | Safety and Efficacy of SMART101 in Adult ... The purpose of this study is to evaluate the safety and the efficacy of SMART101 (Human T Lymphoid Progenitors (HTLP)) injection to accelerate immune ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124062098

SMART101 Donor T-Lymphoid Progenitors to Accelerate ... SMART101 is a cell therapy using allogeneic CD7+ T-lymphoid progenitors (TLP) produced in culture from mobilized peripheral blood CD34+ cells.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/393836

Safety and Efficacy of SMART101 in Adult Patients With ... The purpose of this study is to evaluate the safety and the efficacy of SMART101 (Human T Lymphoid Progenitors (HTLP)) injection to ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-02250

Safety and Efficacy of SMART101 in Pediatric and Adult ... The purpose of this study is to evaluate the safety and the efficacy of SMART101 (Human T Lymphoid Progenitor (HTLP)) injection to accelerate immune ...