CD45RA Depleted Stem Cell Addback for Leukemia

Overseen By Linda Zitkus, BSN,RN

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Children's Hospital of Philadelphia

Must not be taking: Alemtuzumab

Disqualifiers: Hodgkin lymphoma, Non-Burkitt lymphoma, others

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

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with certain blood cancers requiring a stem cell transplant. The study tests whether adding back a special type of T cell from the donor, known as CD45RA Depleted Stem Cell Addback, can accelerate immune system recovery and reduce infection risk post-transplant. Suitable candidates for this trial include those with blood cancers curable by a stem cell transplant who lack a perfectly matched sibling donor. As a Phase 1, Phase 2 trial, this research aims to understand the treatment's function in participants and assess its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking medical advancements.

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 treatment is likely to be safe?

Research has shown that a new treatment called CD45RA Depleted Stem Cell Addback holds promise for treating leukemia. This treatment reduces the risk of graft-versus-host disease (GVHD), a common issue in stem cell transplants. In earlier studies, patients who received this treatment had survival rates of around 60%, comparable to transplants from unrelated donors.

The treatment also aims to preserve important immune cells, reducing transplant complications and improving survival. One study found that CD45RA depletion lowered the risk of viral infections, a serious concern after transplants.

As this trial is in its early stages, the treatment is still being tested for safety in humans. Its current testing phase suggests some safety in earlier research. If it were dangerous, it wouldn't have reached this stage. Always consult a healthcare provider about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for leukemia?

Researchers are excited about the CD45RA Depleted Stem Cell Addback treatment because it offers a novel approach to fighting leukemia by using specialized stem cells. Unlike standard leukemia treatments, which often rely on chemotherapy or radiation, this method focuses on using mobilized peripheral blood stem cells (PBSC) that are carefully depleted of CD45RA. This technique aims to reduce the risk of graft-versus-host disease (GVHD), a common complication in stem cell transplants. Additionally, the treatment utilizes mismatched related donors, which could broaden the pool of available donors, making transplants accessible to more patients. By targeting the immune response more precisely, this treatment holds the potential to improve outcomes for leukemia patients.

What evidence suggests that CD45RA Depleted Stem Cell Addback might be an effective treatment for leukemia?

Research has shown that a technique called CD45RA depleted stem cell addback, which participants in this trial will receive, can enhance immune system recovery. By selectively removing CD45RA cells (or naive T cells), this method increases donor memory T cells, crucial for fighting infections. Studies have found that this approach speeds up T-cell recovery, reducing the risk of blood-borne viruses. Additionally, it has been linked to a decrease in cancer cells, offering hope for treating leukemia. Overall, early evidence suggests that CD45RA depletion leads to a faster and stronger rebuilding of the immune system. ^{4 5 6 7 8}

Who Is on the Research Team?

Timothy Olson, MD, PhD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for individuals up to 25 years old with conditions like primary immunodeficiency, various leukemias, bone marrow failure, and other related disorders. They should be in a state where a stem cell transplant could cure them and meet specific health standards set by the CHOP CTTS program.

Inclusion Criteria

My organs are healthy and I don't have infections.

I have taken a pregnancy test and it was negative.

My condition may be cured by a stem cell transplant from a donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose escalation study to determine the maximum tolerated cell dose of the CD45RA depleted addback using mismatched/haploidentical related donors

Up to 100 days

Phase 2 Treatment

Treatment with CD45RA depleted addback at maximum tolerated dose found in Phase 1 using mismatched related donors and unrelated donors

Concurrent with Phase 1

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of immune reconstitution and graft vs host disease

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• CD45RA Depleted Stem Cell Addback

Trial Overview The study tests adding back CD45RO memory T lymphocytes after depleting certain cells from donor stem cell grafts to prevent GVHD and infections post-transplant. It's determining the safest dose level that accelerates immune recovery without significant side effects.

How Is the Trial Designed?

Group I: Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback using unrelated donors Experimental Treatment 1 Intervention

Stem cell source: mobilized PBSC Donor type: 9/10 or 10/10 matched unrelated donor Conditioning: disease specific SOC regimens

Group II: Phase 2:TCRab/CD19 depleted PSCT with CD45RA depleted addback at MTD found in phase 1 using MMRD Experimental Treatment 1 Intervention

Stem cell source: mobilized PBSC Donor type: \> or = 5/10 mismatched related donor Conditioning: disease specific SOC regimens

Group III: Phase 1:TCRab/CD19 depleted PSCT with CD45RA depleted addback using mismatched related donors (MMRD) Experimental Treatment 3 Interventions

Stem cell source: mobilized peripheral blood stem cells (PBSC) Donor type: \> or = 5/10 mismatched related donor Conditioning: disease specific standard of care (SOC) regimens

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

CD19 CAR T-cell therapy has shown a high complete remission rate in pediatric acute lymphoblastic leukemia, highlighting its efficacy as a treatment for this type of cancer.

Despite its effectiveness, CD19 CAR T-cell therapy is associated with significant adverse reactions and an increased risk of cancer recurrence, necessitating further research into mechanisms of recurrence and strategies to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cluster of differentiation 19 chimeric antigen receptor T-cell therapy in pediatric acute lymphoblastic leukemia. Fu, Z., Zhou, J., Chen, R., et al.[2020]

Allogeneic CAR-engineered CD45RA-negative T cells effectively target and kill CD19(+) MLL-rearranged leukemia cells, showing promise as a cancer treatment without causing graft-versus-host disease (GVHD).

In mouse models, these CAR(+)CD45RA(-) T cells not only reduced leukemia burdens and improved survival but also maintained their ability to respond to infections, suggesting they could be used safely in non-transplant settings as off-the-shelf therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity. Chan, WK., Suwannasaen, D., Throm, RE., et al.[2021]

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]

In a study involving nine patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) and low donor chimerism after allogeneic stem cell transplant, autologous anti-CD19 CAR T cell therapy successfully restored complete donor chimerism in vitro after 12 days of culture.

The therapy showed strong cytotoxic effects against leukemia cells, with most patients experiencing mild cytokine release syndrome as the main adverse event, and two out of three treated patients achieving complete response without acute graft-versus-host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Level Donor Chimerism of CD19 CAR-T Cells Returned to Complete Donor Chimerism in Patients with Relapse After Allo-Hematopoietic Stem Cell Transplant. Li, Q., Mu, J., Yuan, J., et al.[2022]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5809307/

Selective T-cell depletion targeting CD45RA reduces viremia ... CD45RA-depletion provided a large number of donor memory T cells to the recipients, and was associated with enhanced early T-cell recovery and protection ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03810196

CD45RA Depleted Peripheral Stem Cell Addback for Viral ... An addback of donor CD45RA (naive T cells) depleted cells may improve immune reconstitution and help decrease the risk of infections.

3. withpower.com withpower.com/trial/phase-2-mycoses-2-2025-97bfa

CD45RA Depleted Stem Cell Addback for Leukemia Research shows that purging leukemia stem cells from transplants, similar to the CD45RA depletion method, can significantly reduce tumor cells and help in ...

4. astctjournal.org astctjournal.org/article/S2666-6367(21)00753-3/fulltext

Feasibility and Efficacy of CD45RA+ Depleted Donor ... In this prospective phase 2 study, we showed that infusions of multiple CD45RA+ depleted DLI was effective in reducing the risk of viral infections during the ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025028204

TCRαβ-Depleted Haploidentical Stem Cell Transplantation ... CD45RA-depleted memory donor lymphocytes were administered at escalating doses ranging from 25′103/kg to 1000′103/kg at periodic intervals to accelerate immune ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06839456

Phase 1/2: CD45RA Depleted Stem Cell Addback to ... CD45RA depletion has been studied both as a single step to reduce the risk of GVHD, and also, in conjunction with αβTCR depleted hematopoietic stem cell grafts ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9911795/

Selective depletion of naïve T cells by targeting CD45RA - PMC Overall survival was 60% and was comparable to that with transplantation from unrelated donors. Although the results of this study are ...

8. withpower.com withpower.com/trial/phase-leukemia-myelomonocytic-juvenile-2-2019-abf87

Stem Cell Addback for Leukemia Additionally, CD45RA depletion helps preserve important immune cells, improving survival outcomes by reducing transplant-related mortality.