CAR T-Cell Therapy for Leukemia and Lymphoma

Overseen By Clelie Peck

Age: < 65

Sex: Any

Trial Phase: Phase < 1

Sponsor: Nationwide Children's Hospital

Disqualifiers: Neurologic toxicity, Untreated infection, Genetic syndrome, GVHD, others

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

Compensation: Varies

Number of Visits: 1

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot study examines the safety and efficacy of anti-CD19 CAR T cells manufactured on-site in children and young adults with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or CD19+ B cell non Hodgkin lymphoma. Patients will undergo screening, leukapheresis (cell collection), lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by the anti-CD19 CAR T cell infusion. The lymphodepleting chemotherapy is administered over four days IV to prepare the body for the CAR T cells. The anti-CD19 CAR-T cells are infused between 2-14 days after the last dose of chemotherapy. This study is designed for participants to begin lymphodepleting chemotherapy during the CAR T cell manufacture and receive a fresh cell infusion on the day that manufacturing is complete. Some patients may need more time in between the cell collection and the CAR T cell infusion, therefore, the cells may be manufactured and frozen prior to administration. Patients will be followed for a year after the cell infusion on the study and for up to 15 years to monitor for potential long term side effects of cell 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. However, since the trial involves chemotherapy and CAR T-cell therapy, it's possible that some medications might need to be adjusted. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of this treatment for leukemia and lymphoma?

CAR T-cell therapy targeting CD19 has shown remarkable results, achieving complete remission in up to 90% of patients with relapsed or chemotherapy-resistant B-cell acute lymphoblastic leukemia, compared to a 30% response rate with chemotherapy. This success suggests potential effectiveness for other similar blood cancers like lymphoma. ^{1 2 3 4 5}

Is CAR T-Cell Therapy safe for humans?

CAR T-Cell Therapy, including CD19 specific treatments, has shown safety concerns such as cytokine release syndrome (a severe immune reaction), neurotoxicity (nerve damage), and increased risk of infections. These side effects are common but can be managed with proper medical care. ^{6 7 8 9 10}

How is CAR T-Cell Therapy for Leukemia and Lymphoma different from other treatments?

CAR T-Cell Therapy is unique because it involves modifying a patient's own T cells to specifically target and attack cancer cells expressing the CD19 marker, which is not a feature of traditional chemotherapy. This personalized approach has shown remarkable success in achieving complete remission in patients with certain types of leukemia and lymphoma who did not respond to other treatments. ^{1 2 3 4 11}

Research Team

Margaret Lamb, MD

Principal Investigator

Nationwide Children's Hospital

Eligibility Criteria

This trial is for children and young adults up to age 30 with relapsed or refractory CD19+ B cell acute lymphoblastic leukemia or non-Hodgkin lymphoma. Participants must have a certain level of heart, liver, kidney, and lung function, agree to use contraception if applicable, and not be pregnant. They can't join if they have HIV/AIDS, uncontrolled infections including hepatitis B/C, recent graft versus host disease after a transplant, any prior CD19 CAR T cell therapy or are part of another investigational study within the last month.

Inclusion Criteria

I was diagnosed with my condition before turning 31.

My child has B-Cell ALL that has not responded to treatment.

My parent or guardian has signed the consent form for me.

Exclusion Criteria

I have no major ongoing nerve-related issues except for controlled seizures or stable conditions.

I do not have active hepatitis B or C, nor any uncontrolled infections.

HIV positive test within 8 weeks of screening

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Collection of autologous lymphocytes from the patient via apheresis

1 day

1 visit (in-person)

Lymphodepleting Chemotherapy

Administration of fludarabine and cyclophosphamide to prepare the body for CAR T cell infusion

4 days

Inpatient stay

CAR T Cell Infusion

Infusion of anti-CD19 CAR T cells after lymphodepleting chemotherapy

1 day

Inpatient stay

Immediate Post-Infusion Monitoring

Patients are monitored for toxicity including cytokine release syndrome, neurologic toxicity, and tumor lysis syndrome

7 days

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Long-term Follow-up

Monitoring for potential long-term side effects of cell therapy

Up to 15 years

Treatment Details

Interventions

• CD19 specific Chimeric Antigen Receptor T Cell

Trial Overview The trial tests anti-CD19 CAR T cells made on-site for safety and effectiveness against specific blood cancers. It involves screening patients followed by chemotherapy to prepare their bodies before infusing these engineered immune cells. The process includes collecting patient's cells (leukapheresis), giving chemo drugs fludarabine/cyclophosphamide over four days then infusing the CAR T cells between day 2-14 post-chemo.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Leukopharesis: cells collected with a target of ≥1 x10\^9 TNC with ≥3% CD3+ cells. Lymphodepleting chemotherapy: 4 days of IV chemotherapy with fludarabine and cyclophosphamide. * Fludarabine 30 mg/m2/day IV x 4 days (days -6 through -3) * Cyclophosphamide 500 mg/m2/day IV x 2 days (days -6 and-5) anti-CD19 CAR T cells: * 0.3 - 1 x 10\^6 per kilogram for patients \<50 kg * Flat dose of 0.3 - 1 x 10\^8 for patients ≥50 kg The cell infusion will take place on day 0 (at least 2 days after completion of lymphodepleting chemotherapy). The patient will receive pre-medication with acetaminophen and diphenhydramine 30-60 minutes prior to the cell infusion.

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

Findings from Research

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 shown remarkable success in treating B-cell acute lymphoblastic leukemia by targeting the CD19 marker, which is present on most B-cell tumors.

The therapy is being explored for other B-cell malignancies, including chronic lymphocytic leukemia and various types of lymphoma, although challenges remain in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? Pegram, HJ., Smith, EL., Rafiq, S., et al.[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]

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]

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-cell therapy is a groundbreaking treatment for recurrent B-cell lymphomas and acute lymphoid leukemia, showing over 80% remission rates and faster responses compared to traditional therapies, with a treatment duration of just 2-3 weeks.

While CAR T-cell therapy can lead to significant side effects like cytokine release syndrome and neurotoxicity, understanding these potential adverse events and their timelines is crucial for optimizing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists. de Groot, PM., Arevalo, O., Shah, K., et al.[2022]

In a study of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., et al.[2023]

CD19CAR-T cell therapy is effective in treating relapsed and refractory B-lineage acute lymphoblastic leukemia, with four out of five patients achieving complete remission and minimal residual disease negativity.

The therapy can be safely administered with real-time monitoring of a 6-cytokine pattern, allowing for effective management of side effects like cytokine release syndrome and neurotoxicity using tocilizumab and steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy can be administered safely under the real-time monitoring of Th1/Th2 cytokine pattern using the cytometric bead array technology for relapsed and refractory acute lymphoblastic leukemia in children. Shen, D., Song, H., Xu, X., et al.[2021]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

In a Phase I trial involving 43 pediatric and young adult patients with leukemia, initial treatment failures were linked to poor CAR T cell expansion and rapid loss of functional CAR T cells after infusion.

For patients who achieved remission, the durability of that remission was associated with higher levels of TNF-α-secreting CAR CD8+ T cells and sufficient CD19 antigen levels at the time of treatment, suggesting these factors could help predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR T cell product and disease attributes predict leukemia remission durability. Finney, OC., Brakke, HM., Rawlings-Rhea, S., et al.[2022]

References

1. 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]

2. 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]

3. England pubmed.ncbi.nlm.nih.gov

CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. [2023]

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

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

6. 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]

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

Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists. [2022]

8. Denmark pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy can be administered safely under the real-time monitoring of Th1/Th2 cytokine pattern using the cytometric bead array technology for relapsed and refractory acute lymphoblastic leukemia in children. [2021]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

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

CD19 CAR T cell product and disease attributes predict leukemia remission durability. [2022]