Stem Cell Transplant for Leukemia and Lymphoma

Overseen By Beate Greer

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Disqualifiers: Uncontrolled infection, Recent transplant, aGVHD, 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

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

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to make stem cell transplants safer and more effective for people with certain types of leukemia and lymphoma. It involves removing specific immune cells from donated stem cells to reduce complications, using the Miltenyi CliniMACS Prodigy® system. This study targets individuals with conditions like acute lymphocytic leukemia or chronic myeloid leukemia who have not responded to other treatments. Participants must have a matched stem cell donor and healthy organ function. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

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 study team or your doctor to get a clear answer based on your specific situation.

What prior data suggests that the Miltenyi CliniMACS Prodigy® system is safe for stem cell transplantation?

Research has shown that using the Miltenyi CliniMACS Prodigy system for stem cell transplants appears safe. Studies have found that removing certain T-cells and B-cells from donor stem cells is a reliable process that consistently works well, reducing the risk of immune reactions after the transplant.

Additionally, other studies have reported good results with these specially treated stem cells, indicating that the treatment is generally well-tolerated. While still under testing, current evidence suggests a positive safety profile for this type of stem cell transplant. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Miltenyi CliniMACS Prodigy® system for stem cell transplants in leukemia and lymphoma because it offers a novel way to prepare donor cells. Unlike traditional methods, this system depletes ⍺/β CD3+ T-cells and CD19+ B-cells, which might reduce the risk of graft-versus-host disease, a common complication in transplants. By selectively removing these cells, the treatment aims to improve patient safety and outcomes, potentially leading to a more effective and safer transplant process compared to existing therapies.

What evidence suggests that the Miltenyi CliniMACS Prodigy® system is effective for leukemia and lymphoma?

Research has shown that using the Miltenyi CliniMACS Prodigy system to remove specific immune cells, such as certain T-cells and B-cells, can make stem cell transplants safer and more effective. In this trial, participants will receive an allogeneic stem cell transplant with ⍺/β CD3+ T-cell and CD19+ B-cell depleted grafts using this system. One study found that this method led to very good results for patients receiving donor stem cells. The system lowers the risk of complications by selectively removing cells that might cause harmful reactions. This approach has proven reliable and easy to manage, making it a promising option for people with leukemia and lymphoma. Early results suggest it could improve the chances of a successful transplant. ^{1 2 3 4 6}

Who Is on the Research Team?

Jordan Milner, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for patients with certain blood cancers like ALL, AML, CML, lymphoma and high-risk MDS. Participants should be in specific stages of their disease such as first or second remission or have a limited amount of cancer cells in the bone marrow. It's not open to those who don't meet these specific conditions.

Inclusion Criteria

Children, Adolescents, Young adults (ages 6 months to ≤39 years) with the following diseases may be eligible: ALL high risk, ALL in second remission and beyond, AML induction/reinduction Failure, AML in CR1 with poor cytogenetics, AML with persistent minimal residual disease, AML CR2 or beyond, AML in refractory relapse, Therapy-related AML, Juvenile MyeloMonocytic Leukemia (JMML) in CR1 without CBL mutation, JMML with recurrence of disease, JMML CR2 or beyond, Chronic Myeloid Leukemia (CML) in CR with regard to blast crisis, High Risk Myelodysplastic syndrome (MDS), Lymphoma: Hodgkin (HL) or Non-Hodgkin (NHL), Subjects must not have more than one active malignancy at the time of enrollment, HLA-matched sibling donor, matched unrelated donor available for stem cell donation, haplo-identical related donor, Karnofsky or Lansky score ≥60% at the time of enrollment, Adequate organ function, Written informed consent obtained from the subject or guardian, Subjects of childbearing potential using adequate contraception, Subjects with partners of child-bearing potential using physician-approved contraceptive methods

Exclusion Criteria

I am currently pregnant or breastfeeding.

I am not using or cannot use birth control.

I don't have any health conditions that would make the treatment risky for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transplantation

Participants receive an allogeneic stem cell transplant depleted of ⍺/β CD3+ T-cells and CD19+ B-cells

Immediate

Post-Transplant Monitoring

Participants are monitored for acute graft versus host disease (aGVHD) and other outcomes

100 days

Weekly visits

Follow-up

Participants are monitored for overall survival, event-free survival, and viremia incidences

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Miltenyi CliniMACS Prodigy ® system

Trial Overview The study tests a stem cell transplant technique using the Miltenyi CliniMACS Prodigy system to remove certain immune cells (⍺/β CD3+ T-cells and CD19+ B-cells) from donor cells before transplantation into patients with various malignant diseases.

How Is the Trial Designed?

Group I: Allogeneic stem cell transplant with ⍺/β CD3+ T-cell and CD19+ B-cell depleted graft Experimental Treatment 1 Intervention

Miltenyi CliniMACS Prodigy ® system is already approved in United States, European Union for the following indications:

Approved in United States as Miltenyi CliniMACS Prodigy for:

• Acute lymphocytic leukemia (ALL)
• Acute myeloid leukemia (AML)
• Juvenile myelomonocytic leukemia (JMML)
• High risk myelodysplastic syndrome (MDS)
• Chronic myeloid leukemia (CML)
• Lymphoma

Approved in European Union as Miltenyi CliniMACS Prodigy for:

• Acute lymphocytic leukemia (ALL)
• Acute myeloid leukemia (AML)
• Juvenile myelomonocytic leukemia (JMML)
• High risk myelodysplastic syndrome (MDS)
• Chronic myeloid leukemia (CML)
• Lymphoma

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Florida Department of Health

Collaborator

Trials

30

Recruited

13,000+

Ocala Royal Dames for Cancer Research

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

The CliniMACS Prodigy can effectively select CD34+ cells from mobilized peripheral blood stem cell concentrates, achieving a high proportion of CD34+ cells similar to the semiautomated CliniMACS Plus Instrument.

However, the recovery rate of CD34+ cells and the depletion of unwanted CD3+ cells were lower with the automated Prodigy compared to the semiautomated method, indicating potential areas for improvement in the automated process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates. Stroncek, DF., Tran, M., Frodigh, SE., et al.[2021]

The CliniMACS Prodigy system allows for a complete recovery (100%) of CD34+ cells after selection, which is crucial for hematology patients undergoing treatment.

This optimization in cell recovery can significantly enhance the effectiveness of therapies that rely on CD34+ cells, improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal large-scale CD34+ enrichment from a leukapheresis collection using the clinimacs prodigy platform. Pello, OM., Lanzarot, D., Colorado, M., et al.[2020]

The CliniMACS Prodigy system successfully produced 28 CAR T-cell products for heavily pre-treated patients, with 27 meeting all quality specifications, demonstrating its feasibility for clinical-grade manufacturing in a phase I trial for CD19+ B-cell malignancies.

Despite slower expansion rates in patient-derived cells compared to healthy donors, the CAR T-cells exhibited effective cytotoxic activity and a significant proportion (38.7%) had a TCM phenotype, which is associated with long-lasting immune memory, suggesting potential for improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial. Castella, M., Caballero-Baños, M., Ortiz-Maldonado, V., et al.[2021]

The CliniMACS Plus Instrument effectively isolates hematopoietic progenitor cells (HPCs) and other immune cells, achieving viable cell recovery rates between 32.3% and 65.4%, with the highest recovery for CD34+ selections.

Cell purity was notably high, ranging from 86.3% to 99.0%, particularly for CD4+ selections, indicating that the instrument is reliable for preparing cellular therapies, with optimization possible through adjustments in manufacturing variables.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust Selections of Various Hematopoietic Cell Fractions on the CliniMACS Plus Instrument. Panch, SR., Reddy, OL., Li, K., et al.[2021]

The CliniMACS Prodigy® system successfully performed TCRαβ+ T cell and B cell depletion in ten haploidentical stem cell transplants, achieving a median log reduction of TCRαβ+ cells of -4.21, indicating effective cell removal.

The procedure demonstrated reliability and ease of use, with a median CD34 recovery of 83%, although B cell depletion was slightly less efficient with a median log reduction of -3.72.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depletion of αβ+ T and B Cells Using the CliniMACS Prodigy: Results of 10 Graft-Processing Procedures from Haploidentical Donors. Haastrup, E., Ifversen, MRS., Heilmann, C., et al.[2022]

In a study of 159 children with leukemia undergoing T-cell depleted haploidentical transplantation, there were no significant differences in transplant outcomes between the two techniques (CD3+/CD19+ vs TCRαβ+/CD19+), indicating that both methods are equally effective.

Key factors influencing better disease-free survival included early disease status at transplant, presence of chronic graft-versus-host disease (cGvHD), and donor KIR-B genotype, rather than the specific T-cell depletion platform used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-Cell Depleted Haploidentical Transplantation in Children With Hematological Malignancies: A Comparison Between CD3+/CD19+ and TCRαβ+/CD19+ Depletion Platforms. Gonzalez-Vicent, M., Molina, B., Lopez, I., et al.[2022]

The CliniMACS device effectively depleted TCRαβ(+) T cells by an average of 4.7 logs and B cells by 4.1 logs, achieving very low residual levels of these cells in apheresis products, which is crucial for certain therapeutic applications.

The recovery rates for key cell types post-separation were high, with 73% for CD34(+) stem cells and 80% for natural killer cells, while maintaining a cell viability of 98%, indicating that the CliniMACS system is both effective and safe for preparing cell products for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Depletion of T-cell receptor alpha/beta and CD19 positive cells from apheresis products with the CliniMACS device. Schumm, M., Lang, P., Bethge, W., et al.[2020]

Citations

1. miltenyibiotec.com miltenyibiotec.com/US-en/products/clinimacs-tcra-b-product-line.html

CliniMACS® TCRα/β Product Line The variable region of the TCRα/β is involved in recognition of antigenic peptides presented by the MHC complex of antigen-presenting cells. The TCRα/β is ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04249830

NCT04249830 | Stem Cell Transplant From Donors After ... The purpose of the CliniMACS® TCRαβ-Biotin System and CliniMACS® CD19 is to improve the safety and efficacy of allogeneic HLA-partially matched related or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6944939/

Depletion of αβ+ T and B Cells Using the CliniMACS Prodigy Overall, we found the TCRαβ and CD19 depletion procedure on the CliniMACS Prodigy easy to handle and reliable, providing reproducible good ...

4. translational-medicine.biomedcentral.com translational-medicine.biomedcentral.com/articles/10.1186/s12967-023-04738-8

Automatic generation of alloreactivity-reduced donor ... Very satisfactory transplant outcomes were thus reported for TCRαβ/CD19-depleted hematopoietic stem/progenitor cell (HSPC) grafts. The current ...

5. miltenyibiotec.com miltenyibiotec.com/US-en/applications/by-research-area/cell-and-gene-therapy/allogeneic-cell-therapies.html

Enabling allogeneic cell therapy manufacturing Our CliniMACS® Instruments, consumables, and reagents provide essential tools needed to achieve optimal growth conditions and create streamlined scalable ...

6. miltenyibiotec.com miltenyibiotec.com/US-en/applications/by-cell-type/t-cells/t-cell-depletion-in-graft-engineering.html

T cell depletion | Miltenyi Biotec | USA Numerous studies confirm the improved performance of grafts modified via CliniMACS TCRα/β+ and CD19+ depletion in different applications. This includes ...