CAR T-Cell Therapy for Leukemia and Lymphoma

Recruiting at 3 trial locations

Overseen By Corinne Summers, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Seattle Children's Hospital

Disqualifiers: Active malignancy, CNS pathology, GVHD, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

42 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR T-cell therapy for individuals with leukemia or lymphoma that hasn't responded to other treatments. The goal is to determine if a patient's own immune cells, modified to target cancer cells, can be used safely and effectively against these diseases. The trial consists of two parts: first, to find a safe dose, and second, to evaluate the treatment's effectiveness. Eligible participants have leukemia or lymphoma that persists or recurs despite standard treatments, and they must be able to undergo the process of collecting their immune cells. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. You need to be at least 7 days past your last chemotherapy, biologic therapy, and corticosteroid therapy, 3 days past Tyrosine Kinase Inhibitor use, and 1 day past hydroxyurea.

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

Research shows that SCRI-CAR22v2, a type of CAR T-cell therapy, is under study to determine its safety for people with leukemia and lymphoma. In earlier studies, patients seemed to tolerate this treatment well. Early results from the PLAT-07 trial, which tests SCRI-CAR22v2, indicate that side effects can be managed. However, as this treatment remains in the early stages, the primary goal is to ensure its safety and establish the correct dose. While detailed safety information is not yet available, its progression through various trial stages suggests confidence in its potential safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for leukemia and lymphoma, which often include chemotherapy and radiation, SCRI-CAR22v2 is a type of CAR T-cell therapy that offers a unique approach. Researchers are excited because this therapy involves reprogramming a patient’s own immune cells to specifically target and destroy cancer cells. This personalized approach not only aims to enhance effectiveness but also potentially reduces the harsh side effects associated with traditional treatments. By harnessing the body’s immune system, SCRI-CAR22v2 could offer a more precise and potentially more effective option for patients battling these cancers.

What evidence suggests that this CAR T-cell therapy might be an effective treatment for leukemia and lymphoma?

Research has shown that anti-CD22 CAR-T cell therapy, such as SCRI-CAR22v2, effectively treats certain blood cancers, including leukemia and lymphoma. One study found that 80% of patients with acute lymphoblastic leukemia (ALL) experienced complete remission, with their cancer becoming undetectable, and 51% remained alive after one year. SCRI-CAR22v2, which participants in this trial will receive, is an improved version of the original treatment, offering enhanced activity and survival outcomes. This therapy uses specially modified T cells to locate and attack cancer cells by targeting a protein called CD22. Researchers are further studying this promising method to confirm its effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Corinne Summers, MD

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

This trial is for young individuals up to 30 years old with stubborn leukemia or lymphoma that hasn't responded to other treatments. They must have a certain protein (CD22) on their cancer cells, be able to handle the procedure to collect immune cells, and not be pregnant or breastfeeding. Those who've had previous CAR T cell therapy can join if they meet other health requirements.

Inclusion Criteria

Life expectancy ≥ 8 weeks

It's been over a week since my last chemotherapy or biologic therapy.

Subjects of childbearing or child-fathering potential must agree to use highly effective contraception from consent through 12 months following infusion of investigational product on trial

Exclusion Criteria

I am currently suffering from a severe infection.

I have previously undergone virotherapy.

My cancer cells all show CD19 and I haven't tried CD19 CAR T cell therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive genetically modified T cells (SCRI-CAR22v2) targeting CD22 for relapsed/refractory leukemia or lymphoma

28 days

Multiple visits for T cell infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after T cell infusion

4 weeks

Regular follow-up visits to assess response and adverse events

Long-term follow-up

Participants are monitored for long-term safety and efficacy of the CAR T cell therapy

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• SCRI-CAR22v2

Trial Overview The study tests genetically modified T cells targeting CD22 in patients with tough-to-treat leukemia or lymphoma. It's split into two parts: first finding a safe dose of these CAR T cells and then checking how well they work against the cancer.

How Is the Trial Designed?

Group I: SCRI-CAR22v2 Experimental Treatment 1 Intervention

Patients will receive SCRI-CAR22v2 in either Phase I or Phase II

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Published Research Related to This Trial

In a phase I trial involving 12 younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, the use of chimeric antigen receptor T cells targeting CD19 and CD22 showed manageable toxicity levels.

Out of the 12 patients, 5 achieved complete responses, indicating promising efficacy of this treatment approach in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]

CAR T cell therapy has evolved over 30 years through four generations of innovation, enhancing its ability to treat difficult-to-treat blood cancers by improving its structure with multiple co-stimulatory molecules.

This therapy allows T cells to specifically target tumor antigens without being limited by the body's major histocompatibility complex (MHC), representing a significant advancement in the treatment of hematologic malignancies like leukemia and multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current Status and Challenges of CAR-T Immunotherapy in Hematologic Malignancies -Review]. Cheng, X., Wang, YJ., Feng, S., et al.[2018]

In a study of 13 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and B cell acute lymphoid leukemia (B-ALL) who previously failed anti-CD19 CAR T cell therapy, anti-CD22 CAR T cell salvage therapy resulted in a higher complete response rate in DLBCL patients, with 4 achieving complete response compared to only 2 in B-ALL.

The anti-CD22 CAR T cell therapy was associated with lower grades of cytokine release syndrome (CRS) compared to the previous anti-CD19 therapy, indicating a potentially safer profile, while overall survival for DLBCL patients was approximately 6.1 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR-T Cell Therapy as a Salvage Treatment in B Cell Malignancies Refractory or Relapsed After Anti-CD19 CAR-T therapy. Zhu, H., Deng, H., Mu, J., et al.[2022]

CAR T-cell therapy has received FDA approval for treating relapsed/refractory diffuse large B-cell lymphoma, recurrent acute lymphoblastic leukemia, and mantle cell lymphoma, highlighting its growing role in hematological cancer treatment.

Despite its promise, CAR T-cell therapy faces challenges in efficacy and persistence across different hematological malignancies, with over a thousand ongoing clinical trials aimed at addressing these issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies. Lin, WY., Wang, HH., Chen, YW., et al.[2021]

CAR-T therapy has shown promising results in treating leukemia and lymphoma, offering potentially curative options for patients who previously had limited treatment choices, as highlighted in studies presented at the 61st annual meeting of the American Society of Hematology.

Recent advancements in CAR-T constructs aim to enhance treatment efficacy and durability while also improving strategies to manage toxicity, indicating a focus on both effectiveness and patient safety in the evolving field of cellular immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates in Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Lymphoma and Leukemia from the Annual Meeting of American Society of Hematology 2019. Bukhari, A., Siglin, J., Lutfi, F., et al.[2020]

In a review of 35 studies involving 1412 patients with acute lymphocytic leukemia (ALL) and lymphoma treated with CD19 CAR-T cell therapy, severe cytokine release syndrome (sCRS) occurred in 18.5% of patients, highlighting a significant side effect of this treatment.

The incidence of sCRS was notably higher in patients under 18 years old (28.6%) compared to those over 18 (16.1%), suggesting that age may influence the risk of this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The incidence of cytokine release syndrome and neurotoxicity of CD19 chimeric antigen receptor-T cell therapy in the patient with acute lymphoblastic leukemia and lymphoma. Cao, JX., Wang, H., Gao, WJ., et al.[2020]

CAR-T therapy is highly effective for patients with relapsed/refractory hematologic malignancies, but it also significantly increases the risk of infections due to prolonged immunosuppression and unique toxicities, such as cytokine release syndrome and neurotoxicity.

Patients receiving CAR-T therapy may not respond adequately to SARS-CoV-2 vaccines, highlighting the need for tailored vaccination strategies, including potential booster doses and novel vaccine approaches to enhance immune responses in this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses. Meir, J., Abid, MA., Abid, MB.[2023]

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 and CD20 has shown a promising overall response rate of 61% in treating B-cell hematologic malignancies, with a complete response rate of 42% and partial response rate of 19% across 16 studies involving 195 patients.

However, the therapy is associated with significant adverse events, including cytokine release syndrome and neurotoxicity (both at 33%), and B-cell aplasia in 54% of patients, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD 19 and anti-CD 20 CAR-modified T cells for B-cell malignancies: a systematic review and meta-analysis. Riaz, IB., Zahid, U., Kamal, MU., et al.[2023]

A first-in-human trial of anti-CD22 CAR T-cell therapy in children and young adults with relapsed acute lymphocytic leukemia demonstrated that the treatment is feasible, safe, and effective, resulting in remissions for most patients.

The study found that infusing higher numbers of T cells was associated with better treatment responses, suggesting a dose-dependent effect in the therapy's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD22 CAR Therapy Leads to ALL Remissions. [2018]

CAR T-cell therapy has shown durable remission in B-cell leukemia and lymphoma, highlighting its potential effectiveness for treating other types of cancers.

Recent advancements in CAR design and clinical application strategies aim to enhance T-cell proliferation and efficacy while minimizing toxicity, making this therapy more accessible to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cells: New Approaches to Improve Their Efficacy and Reduce Toxicity. Maus, MV., Powell, DJ.[2018]

CD4-specific chimeric antigen receptor (CAR) engineered T cells (CD4CART) demonstrated strong cytotoxic effects against CD4+ T cell lymphoma in both laboratory tests and in live mice, indicating their potential as an effective treatment.

The transfer of CD4CART cells significantly reduced tumor growth and improved survival rates in mice with T cell lymphoma compared to control treatments, suggesting a promising therapeutic approach for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD4-Targeted T Cells Rapidly Induce Remissions in Mice with T Cell Lymphoma. Cheng, J., Chen, G., Lv, H., et al.[2022]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

CD19-targeted CAR-T cell therapy has shown high efficacy in treating relapsed/refractory B-cell malignancies, with recent trials demonstrating impressive initial results and durable responses.

Despite its effectiveness, CAR-T therapy faces significant challenges, including life-threatening side effects like cytokine release syndrome and neurotoxicity, highlighting the need for improved safety measures and further research into targeting other B-cell antigens and solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials for chimeric antigen receptor T-cell therapy: lessons learned and future directions. Schroeder, BA., Jess, J., Sankaran, H., et al.[2023]

CD22-targeting CAR T-cell therapies show high complete response rates, with 68% in acute lymphoblastic leukemia (ALL) and 64% in non-Hodgkin's lymphoma (NHL), indicating their efficacy in treating these malignancies.

The incidence of severe side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), is low, suggesting that these therapies are relatively safe, especially with dual-targeting CAR T-cells not increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. Fergusson, NJ., Adeel, K., Kekre, N., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11070555/

Novel and multiple targets for chimeric antigen receptor-based ... SCRI-CAR22v2 is an improved version of its predecessor SCRI-CAR22v1, with a shorter linker and transmembrane region, and better activity and survival than the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10566133/

Targeting CD22 for B-cell hematologic malignancies - PMC This review focuses on the development, the available clinical data and the strategies to improve the efficacy of CD22-targeted therapies.

3. researchgate.net researchgate.net/publication/370764818_A_systematic_review_and_meta-analysis_of_CD22_CAR_T-cells_alone_or_in_combination_with_CD19_CAR_T-cells

A systematic review and meta-analysis of CD22 CAR T- ... [Show full abstract] ALL patients had a complete remission (CR) rate of 80% and a 1-year overall survival rate of 51%. The graft-versus-host ...

4. scispace.com scispace.com/pdf/car-t-cell-therapies-for-b-cell-lymphoid-malignancies-3bu9iwls.pdf

CAR-T cell Therapies for B-cell Lymphoid Malignancies Chimeric antigen receptors (CARs) are synthetic engineered receptors with an antigen recognition domain derived from a high-speciicity monoclonal antibody ...

5. withpower.com withpower.com/trial/phase-2-lymphoma-8-2020-c8570

CAR T-Cell Therapy for Leukemia and Lymphoma What data supports the effectiveness of the treatment SCRI-CAR22v2 for leukemia and lymphoma? Research shows that anti-CD22 CAR-T cell therapy, similar to SCRI ...

6. seattlechildrens.org seattlechildrens.org/media/press-releases/seattle-childrens-presents-pediatric-cancer-immunotherapy-research-findings-at-american-society-of-hematology-annual-meeting-20212/

Seattle Children's Announces Presentations at the ASH ... As a result, SCRI-CAR22v2 was designed and based on promising preclinical data, PLAT-07 opened for enrollment. In PLAT-07, the CAR T-cells ...