Human-Domain CAR T Therapy for Leukemia and Lymphoma

Not currently recruiting at 1 trial location

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Must not be taking: Immunosuppressants, Virotherapy

Disqualifiers: Active malignancy, CNS pathology, Severe infection, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new therapy called Human-Domain CAR T Therapy for individuals with relapsed or hard-to-treat leukemia or lymphoma. The treatment modifies the patient's own T cells to better fight cancer cells. The goal is to determine if this therapy is safe and can prevent cancer recurrence. Patients with leukemia or lymphoma that returns after treatment and who can undergo a procedure to collect their T cells might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that participants stop certain medications before joining. 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. If you're on maintenance chemotherapy or intrathecal chemotherapy, you may continue those.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments being tested, SCRI-huCAR19v1 and SCRI-huCAR19v2, appear safe so far. Earlier studies on SCRI-huCAR19v1 found that 93% of patients showed no signs of cancer after 21 days, indicating the treatment was well-tolerated.

For SCRI-huCAR19v2, studies have focused on determining the optimal dose and monitoring side effects. Researchers carefully observe patient responses and adjust the treatment to minimize risks.

Both treatments are in early testing stages, with safety as the primary focus. Researchers remain vigilant for any side effects. Overall, early results suggest these treatments are generally safe, but as with any new therapy, risks are being closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SCRI-huCAR19v2 because it represents a new frontier in treating leukemia and lymphoma. Unlike traditional treatments like chemotherapy and radiation, which attack both healthy and cancerous cells, SCRI-huCAR19v2 uses a targeted approach called CAR T-cell therapy. This therapy modifies the patient's own immune cells to specifically recognize and destroy cancer cells with a protein called CD19 on their surface. This precise targeting could mean fewer side effects and a more effective attack on the cancer.

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

Research has shown that CAR T cells, specially designed immune cells, can be effective against leukemia and lymphoma. In this trial, participants may receive either the SCRI-huCAR19v1 or SCRI-huCAR19v2 treatment. A study found that in the SCRI-huCAR19v1 treatment, 93% of patients had no detectable cancer within 21 days, indicating that most patients went into complete remission. Meanwhile, the SCRI-huCAR19v2 treatment has shown promise, with 69.5% of patients surviving for at least one year. These treatments target a protein called CD19 on cancer cells, enabling the immune system to attack the cancer. These early results suggest that these treatments could be effective options for patients with these cancers. ^{1 2 5 6 7}

Who Is on the Research Team?

Colleen Annesley, MD

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

This trial is for young individuals (1-30 years old) with CD19+ leukemia or lymphoma that hasn't responded to other treatments. They must be able to undergo apheresis, have a life expectancy of at least 8 weeks, and use effective contraception. Those with severe infections, primary immunodeficiency, active malignancies besides the study's focus, symptomatic CNS issues uncontrolled by enrollment, or active GVHD are excluded.

Inclusion Criteria

It has been over 30 days since my last CAR T cell treatment.

My organs are working well.

Adequate laboratory values, including absolute lymphocyte count ≥ 100 cells/uL

Exclusion Criteria

I am currently being treated for or have symptoms of GVHD.

I am currently fighting a severe infection.

I have a primary immunodeficiency syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Determine the safety of CD19-specific CAR T cells

4 weeks

Phase 2 Treatment

Determine the effectiveness of CD19-specific CAR T cell therapy

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SCRI-huCAR19v1
• SCRI-huCAR19v2

Trial Overview The trial tests two versions of SCRI-huCAR19 CAR T cells designed to target CD19 on cancer cells. It aims to see if these genetically engineered T cells from patients can treat leukemia/lymphoma without being rejected by the body. The first phase checks safety; the second phase assesses effectiveness.

How Is the Trial Designed?

Group I: SCRI-huCAR19v2 Experimental Treatment 1 Intervention

Patients will receive SCRI-huCAR19v2 in either Phase 1 or Phase II

Group II: SCRI-huCAR19v1 - [CLOSED] Experimental Treatment 1 Intervention

Patients will receive SCRI-huCAR19v1 in either Phase 1 or Phase II. As of 02/13/2020 this study cohort is permanently closed.

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Published Research Related to This Trial

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]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., et al.[2022]

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]

Chimeric antigen receptor (CAR) therapy, particularly targeting CD19, has shown significant efficacy in treating patients with chemorefractory B cell malignancies, leading to its potential regulatory approval as a cell-based immunotherapy.

While CAR therapy is effective, it is associated with toxicities such as cytokine release syndrome, neurotoxicity, and B cell aplasia, which require careful management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. Davila, ML., Sadelain, M.[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]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[2022]

In a phase I clinical trial involving 20 patients with B-cell lymphoma, 55% achieved complete remission using the new anti-CD19 CAR T-cell therapy Hu19-CD828Z, demonstrating its effectiveness against lymphoma.

Hu19-CD828Z therapy resulted in significantly lower rates of severe neurologic toxicity (5%) compared to the previously tested FMC63-28Z therapy (50%), likely due to reduced cytokine release associated with the Hu19-CD828Z CAR design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of anti-CD19 CAR T cells with fully human binding domains in patients with B-cell lymphoma. Brudno, JN., Lam, N., Vanasse, D., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-2-leukemia-10-2018-f58a7

Human-Domain CAR T Therapy for Leukemia and Lymphoma What data supports the effectiveness of the treatment SCRI-huCAR19v1, SCRI-huCAR19v2 for leukemia and lymphoma? Research shows that CAR-T cells with ...

2. researchgate.net researchgate.net/publication/336559130_Long_Term_Follow-up_after_SCRI-CAR19v1_Reveals_Late_Recurrences_As_Well_As_a_Survival_Advantage_to_Consolidation_with_HCT_after_CAR_T_Cell_Induced_Remission

Long Term Follow-up after SCRI-CAR19v1 Reveals Late ... Our Phase 1 clinical trial demonstrated a minimal residual disease (MRD) negative complete remission (CR) rate of 93% at 21 days following SCRI- ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12466217/

real-world outcomes of CD19 CAR T-cell therapy in ... The 1-year progression-free survival rate was significantly better (55.8%; 95% CI, 43.6-66.4) in the TriNHL group than in the de novo LBCL group (31.7%; 95% CI, ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36335261/

Outcomes of first therapy after CD19-CAR-T treatment failure ... We describe outcomes and features following CAR-T treatment failure. Of 305 adults who received CD19-CAR-T, 182 experienced disease recurrence ...

5. go.drugbank.com go.drugbank.com/conditions/DBCOND0006647

Lymphoma (DBCOND0006647) SCRI-huCAR19v1; SCRI-huCAR19v2. treatment, 1 ... Study Evaluating the Efficacy and Safety With CAR-T Immunotherapy for CD19 Positive Lymphoma ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32894185/

Efficacy and safety of CD19 CAR T constructed with a new ... A pilot study was undertaken to assess the safety and feasibility of CNCT19-based therapy in both pediatric and adult patients with relapsed/ ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06596057

Safety and Efficacy of CD19 CAR-T/CAR-NK Cells 15) No central nervous system metastasis was found in patients with central nervous system leukemia and lymphoma (symptoms, signs, imaging, cerebrospinal fluid) ...