CAR T-Cell Therapy for Lymphoma

Overseen By Emerging Medicine

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Pennsylvania

Disqualifiers: Uncontrolled infection, Hepatitis B/C, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is designed to evaluate the effects of retreatment with CTL019/CTL119 in patients with late relapse of B-cell lymphomas.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment CTL019/CTL119 for lymphoma?

CAR T-cell therapy, which includes treatments like CTL019/CTL119, has shown promising results in treating aggressive B-cell lymphomas, with studies reporting high response rates and some patients achieving long-term remission. In one study, a novel CAR T-cell treatment showed a 77.8% overall response rate and a 55.6% complete response rate in patients with refractory/relapsed B-cell lymphoma, indicating its potential effectiveness. ^{1 2 3 4 5}

Is CAR T-cell therapy safe for humans?

CAR T-cell therapy has shown to be generally safe in humans, but it can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage) in some patients. Rare but potentially fatal side effects, such as hemophagocytic lymphohistiocytosis (a severe immune system reaction) and disseminated intravascular coagulation (a blood clotting disorder), have also been reported. ^{1 3 6 7 8}

How is CAR T-cell therapy different from other treatments for lymphoma?

CAR T-cell therapy is unique because it involves modifying a patient's own immune cells to specifically target and attack cancer cells, offering a new option for those with lymphoma that doesn't respond to standard treatments. This therapy has shown impressive results, especially in cases where traditional chemotherapy has failed, by inducing long-lasting remissions in some patients. ^{1 2 9 10 11}

Research Team

Stephen Schuster, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults with B-cell lymphomas who've had a good response to previous CAR T-cell therapy (CTL019/CTL119) lasting at least 6 months. They should have no other curative options and a limited prognosis. Key health requirements include normal liver function, decent heart function, and stable performance status.

Inclusion Criteria

I had a successful CAR T-cell treatment lasting at least 6 months.

Agree to contraceptive requirements outlined in Section 4.3

My lymphoma is CD19 positive.

Exclusion Criteria

I currently have an infection that is not under control.

I am HIV positive.

Any uncontrolled active medical disorder that would preclude participation as outlined

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Retreatment

Participants receive retreatment with CTL019/CTL119 chimeric antigen receptor (CAR) modified T cells

3 months

Follow-up

Participants are monitored for safety and effectiveness after retreatment

12 months

Treatment Details

Interventions

• CTL019/CTL119

Trial Overview The study tests the effects of reusing CTL019/CTL119 cells in patients whose B-cell lymphoma has relapsed late after initial successful treatment. It's for those who previously participated in UPCC13413/NCT02030834 and still have their manufactured product available.

Participant Groups

Group I: Retreatment with CTL019/CTL119 Experimental Treatment 1 Intervention

All subjects will receive retreatment with CTL019/CTL119 and be followed per the schedule of procedures.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Findings from Research

Adoptive cellular therapy using CAR-modified T cells targeting CD19 has shown significant clinical efficacy in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in both children and adults, with some patients also benefiting from treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL).

Current research is expanding the use of CAR T-cell therapies to other cancers, including multiple myeloma and solid tumors, while also addressing challenges such as severe cytokine release syndrome and neurologic toxicities associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. Geyer, MB., Brentjens, RJ.[2022]

CAR T-cell therapy is becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.

The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[2021]

The study developed a CAR (CD4CAR) that enables CD8+ T cells to target and eliminate CD4+ T-cell lymphomas, showing effectiveness in both laboratory and patient-derived samples.

In mouse models of aggressive T-cell lymphoma, CD4CAR T cells not only suppressed tumor growth but also significantly extended survival, suggesting their potential as a new treatment option for patients with peripheral T-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. Pinz, K., Liu, H., Golightly, M., et al.[2018]

A systematic analysis of CAR T-cell therapy adverse events revealed 5,112 reports of hematotoxicity, highlighting significant under-reporting of severe conditions like hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC), which have high mortality rates of 69.9% and 59.6%, respectively.

The study identified 23 hematologic adverse events that were significantly over-reported compared to the general database, emphasizing the need for increased awareness and monitoring of these rare but potentially fatal toxicities in CAR T therapy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. Song, Z., Tu, D., Tang, G., 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]

CAR T-cell therapy, particularly anti-CD19 CAR T cells, shows strong efficacy in treating resistant forms of B-cell lymphomas, achieving durable complete remissions lasting over 2 years in some patients with refractory diffuse large-B-cell lymphoma (DLBCL).

Despite their effectiveness, CAR T-cell therapies can lead to severe toxicities, such as cytokine-release syndrome and neurological issues, highlighting the need for careful management and ongoing research into safer CAR designs and treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapies for lymphoma. Brudno, JN., Kochenderfer, JN.[2022]

Anti-CD19-directed CAR T cell therapy has shown significant efficacy in treating relapsed or refractory B-cell malignancies, leading to the approval of tisagenlecleucel (Kymriah) for B-ALL in 2018 and for aggressive B-cell lymphoma shortly thereafter.

The review highlights ongoing research into resistance mechanisms and the exploration of new target antigens, indicating a continued effort to improve treatment outcomes for patients with CD19 positive B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[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]

References

1. England pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. [2022]

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

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. [2023]

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

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. [2021]

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

Chimeric antigen receptor T-cell lymphoma immunotherapy: the next questions. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Preclinical targeting of human T-cell malignancies using CD4-specific chimeric antigen receptor (CAR)-engineered T cells. [2018]

6. Italy pubmed.ncbi.nlm.nih.gov

Hemophagocytic lymphohistiocytosis and disseminated intravascular coagulation are underestimated, but fatal adverse events in chimeric antigen receptor T-cell therapy. [2023]

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

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

8. China pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy in mature lymphoid malignancies: clinical opportunities and challenges. [2023]

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

Chimeric antigen receptor T-cell therapies for lymphoma. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. [2021]

11. 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]