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

Trial Summary

What is the purpose of this trial?

Patients with relapsed or refractory leukemia or lymphoma are often refractory to further chemotherapy. In this study, the investigators will attempt to use T cells obtained directly from the patient, which can be genetically engineered to express a chimeric antigen receptor (CAR). The CAR used in this study can recognize CD22, a protein expressed on the surface of leukemia and lymphoma cells. The phase 1 part of this study will determine the safety and appropriate dose level of these CAR T cells, and the phase 2 part of the study will determine how effective this CAR T cell therapy is. Both patients who have never had prior CAR T cell therapy and those who have had prior CAR T cell therapy may be eligible to participate in this study.

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.

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-CAR22v2, has been effective in achieving remissions in patients with relapsed or refractory acute lymphocytic leukemia. Additionally, targeting both CD19 and CD22 has led to complete responses in some younger patients with B-cell acute lymphoblastic leukemia. ^{1 2 3 4 5}

Is CAR T-cell therapy generally safe for humans?

CAR T-cell therapy, including those targeting CD19 and CD22, has shown manageable side effects in clinical trials. Common side effects include cytokine release syndrome (CRS) and neurotoxicity, but severe cases are relatively rare. Long-term risks include infections due to weakened immune systems, but overall, the therapy is considered safe with careful monitoring. ^{2 6 7 8 9}

What makes the treatment SCRI-CAR22v2 unique for leukemia and lymphoma?

SCRI-CAR22v2 is a type of CAR T-cell therapy, which is a novel treatment that uses genetically modified T cells to target specific antigens on cancer cells, offering a personalized approach to treating leukemia and lymphoma. Unlike traditional chemotherapy, CAR T-cell therapy can induce remissions in patients with relapsed or refractory conditions by directly targeting and killing cancer cells. ^{10 11 12 13 14}

Research Team

Corinne Summers, MD

Principal Investigator

Seattle Children's Hospital

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

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 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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

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

4. New Zealand 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Clinical trials for chimeric antigen receptor T-cell therapy: lessons learned and future directions. [2023]

6. Switzerland 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. [2023]

7. England 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. [2020]

8. England 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. [2023]

9. United States 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. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

CD4-Targeted T Cells Rapidly Induce Remissions in Mice with T Cell Lymphoma. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

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

13. Netherlands 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. [2020]

14. China pubmed.ncbi.nlm.nih.gov

[Current Status and Challenges of CAR-T Immunotherapy in Hematologic Malignancies -Review]. [2018]