T Cell Immunotherapy for Acute Leukemia

Overseen By FHCC Immunotherapy Intake

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Research Center

Disqualifiers: Grade IV GVHD, Severe chronic GVHD, Life expectancy < 3 months, others

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

Compensation: Varies

Number of Visits: 12

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new type of T cell immunotherapy for individuals with acute leukemia that persists, recurs, or resists treatment after a stem cell transplant. The treatment uses specially designed T cells to recognize and attack leukemia cells by targeting a specific protein called HA-1. The study aims to determine the optimal dose and understand the side effects. It suits those who have undergone a donor stem cell transplant for acute leukemia and still face disease-related challenges. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It seems you may continue other treatments for your disease while participating, but it's best to discuss this with the trial team.

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

Research has shown that special immune cells, called CD4+ and CD8+ T cells, are being tested for safety in treating acute leukemia. These cells are modified in a lab to recognize and attack leukemia cells.

The main goal of these trials is to determine a safe dose and monitor for any side effects. Early results suggest that these T cells can be administered safely. Some patients may experience side effects, but the trials aim to find a dose that minimizes these effects.

It is important to note that this treatment remains in the early testing stages. While some evidence supports its safety, more information is needed to fully understand its effects on patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR because they offer a new way to tackle acute leukemia. Unlike traditional treatments like chemotherapy and bone marrow transplants, which target cancer cells broadly, this immunotherapy is more precise. It uses engineered T cells to specifically recognize and attack leukemia cells, potentially reducing side effects and improving outcomes. This approach harnesses the body's immune system in a powerful and targeted manner, offering hope for more effective and personalized treatment.

What evidence suggests that this trial's treatments could be effective for acute leukemia?

Studies have shown that certain immune cells, called T cells, can be trained to recognize and attack leukemia cells. In this trial, participants will receive CD8+ and CD4+ donor memory T-cells expressing HA1-specific TCR, modified to specifically target leukemia cells with a marker called HA-1. Early findings suggest that these modified T cells can effectively destroy cancer cells in the lab. This approach aims to help the body's immune system better identify and fight leukemia, especially when the cancer has returned or is difficult to treat with other methods. Although human studies have provided limited information, the potential for these T cells to improve treatment outcomes remains promising. ^{1 2 4 6 7}

Who Is on the Research Team?

Elizabeth Krakow

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients aged 0-75 with acute leukemia or myelodysplastic syndrome that's persistent, recurrent, or refractory after a donor stem cell transplant. They must have specific genetic markers (HLA-A*0201 and HA-1(H) genotype). Initially, only those over 16 will receive treatment; younger patients may join but won't be treated until an older patient has been assessed.

Inclusion Criteria

Patients must agree to participate in long-term follow-up for up to 15 years if they are enrolled in the study and receive T cell infusion

My genetic makeup includes HLA-A*0201.

I am between 0 and 75 years old.

Exclusion Criteria

My doctor might delay my treatment due to organ issues, but I can still join the study.

I developed severe GVHD after my most recent transplant.

Unrelated donor residing outside of the United States of America (USA) unless the donor screening, testing and leukapheresis occur at an NMDP-affiliated and qualified donor center and are facilitated by the NMDP

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Patients receive lymphodepleting chemotherapy (e.g., fludarabine and cyclophosphamide) ending 2-14 days prior to HA-1 TCR T cell administration

2-14 days

T Cell Infusion

Patients receive CD4+ and CD8+ HA-1 TCR T cells intravenously

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Close follow-up for 12 weeks, then every 6 months for years 1-5, and every year for years 6-15

What Are the Treatments Tested in This Trial?

Interventions

• CD8+ and CD4+ Donor Memory T-cells-expressing HA1-Specific TCR
• Fludarabine

Trial Overview The trial tests CD4+ and CD8+ T-cells modified to express HA-1-specific TCR against leukemia cells in combination with Fludarabine. It aims to find the safest dose of these genetically engineered T-cells that can recognize and attack cancer cells without harming normal ones.

How Is the Trial Designed?

Group I: Treatment (CD4+ and CD8+ HA-1 TCR T cells) Experimental Treatment 3 Interventions

Patients receive lymphodepleting chemotherapy (e.g., fludarabine and cyclophosphamide or debulking regimens as specified in the protocol) ending 2-14 days prior to HA-1 TCR T cell administration. Patients then receive CD4+ and CD8+ HA-1 TCR T cells IV.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

PromiCell Therapeutics, Inc.

Collaborator

Trials

1

Recruited

50+

HighPass Bio, Inc.

Collaborator

Trials

1

Recruited

20+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03326921

NCT03326921 | HA-1 T TCR T Cell Immunotherapy for the ... This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) (HA-1 T TCR) T cells in treating patients with acute ...

2. ashpublications.org ashpublications.org/blood/article/144/10/1069/515965/HA-1-targeted-T-cell-receptor-T-cell-therapy-for

HA-1–targeted T-cell receptor T-cell therapy for recurrent ... This trial used a class I–restricted TCR and a CD8 coreceptor to enable antigen–specific CD8+ and CD4+ T-cell function.

3. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/cd8-and-cd4-donor-memory-t-cells-expressing-ha1-specific-tcr

Clinical Trials Using CD8+ and CD4+ Donor Memory T- ... Review the clinical trials studying cd8+ and cd4+ donor memory t-cells-expressing ha1-specific tcr on this list and use the filters to refine the results by ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10000933/

Transgenic HA-1-Specific CD8+ T-Lymphocytes ... CD8+ T cells after endogenous TCR knock out and introduction of transgenic HA-1-specific TCR were able to lyse hematopoietic cells from HA-1+ ...

5. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_12004.ha-1-t-tcr-t-cell-immunotherapy-for-the-treating-of-patients-with-relapsed-or-refractory-acute-leukemia-after-donor-stem-cell-transplant.html

HA-1 T TCR T Cell Immunotherapy for the Treating of ... This phase I trial studies the side effects and best dose of CD4+ and CD8+ HA-1 T cell receptor (TCR) T cells in treating patients with acute ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5755045/

Development of T-cell immunotherapy for hematopoietic stem ... A new T-cell immunotherapy has been developed to prevent or manage relapse of leukemia following HCT. Memory CD8+ and CD4+ T cells are engineered with a minor ...

7. researchgate.net researchgate.net/publication/349092294_Phase_I_Study_of_Adoptive_Immunotherapy_with_HA-1-Specific_CD8_and_CD4_Memory_T_Cells_for_Children_and_Adults_with_Relapsed_Acute_Leukemia_after_Allogeneic_Hematopoietic_Stem_Cell_Transplantation_HCT_

Phase I Study of Adoptive Immunotherapy with HA-1- ... Primary end points are 1) Feasibility of manufacturing and administering HA-1 TCR CD8+ and CD4+ memory T cells and 2) Dose-limiting toxicity of ...