T Lymphocyte Therapy for Lymphoma

Not currently recruiting at 1 trial location

Overseen By Caroline Babinec

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: UNC Lineberger Comprehensive Cancer Center

Must not be taking: Anti-CD30 antibodies, Corticosteroids

Disqualifiers: Pregnancy, HIV, HBV, HCV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain types of lymphoma, a cancer affecting the lymphatic system. The treatment combines antibodies, which help the immune system recognize cancer cells, and T cells, which can destroy cancer cells, to create a more powerful therapy. Researchers aim to find a safe dose of these modified T cells, called ATLCAR.CD30 cells (a type of T lymphocyte therapy), and understand their effects on cancer and any potential side effects. Suitable candidates for this trial have lymphoma with CD30+ disease, a specific marker on their cancer cells, and plan to undergo a transplant after high-dose chemotherapy. As a Phase 1 trial, this 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 does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently using systemic corticosteroids at doses of 10mg/day or more, or if you have received certain investigational agents or anti-CD30 antibody-based therapy recently.

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

In earlier studies, anti-CD30 CAR T cells have shown promise in treating lymphoma. These cells combine T cells with a part of an antibody that targets cancer cells. Research suggests these treatments are generally safe. One study found that 62% of patients responded positively, with many experiencing good results. Another study demonstrated excellent safety, with some patients experiencing long-term benefits.

Some side effects have been reported, but they are usually manageable, including mild symptoms like fever and tiredness. Researchers are still determining the best dose, but the treatment appears well-tolerated so far. This trial is in an early phase, focusing on ensuring the treatment's safety for people. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for lymphoma?

Unlike the standard treatments for lymphoma, which often involve chemotherapy and radiation, ATLCAR.CD30 cells utilize a cutting-edge approach called CAR-T cell therapy. This treatment is unique because it involves genetically modifying a patient's own T lymphocytes to better recognize and attack cancer cells expressing the CD30 protein. Researchers are excited about this therapy because it offers a targeted attack on cancer cells, potentially reducing side effects and improving outcomes compared to traditional therapies. Additionally, this personalized approach allows the treatment to adapt to the specific cancer profile of each patient, paving the way for more effective and individualized care.

What evidence suggests that ATLCAR.CD30 cells might be an effective treatment for lymphoma?

Research has shown that ATLCAR.CD30 cells, evaluated in this trial, may help treat lymphoma, a type of cancer. In one study, 62% of patients experienced a response to this treatment. Another study with 151 participants found a similar response rate of 57% for certain types of lymphoma. The treatment proved effective and well-tolerated in patients with Hodgkin lymphoma and anaplastic large cell lymphoma, both types of blood cancer. These results suggest that ATLCAR.CD30 cells could become an important option for fighting lymphoma. ^{1 3 6 7 8}

Who Is on the Research Team?

Natalie Grover, MD

Principal Investigator

Clinical Director of Cellular Therapy Program

Are You a Good Fit for This Trial?

This trial is for patients with certain types of lymphoma, including Hodgkin's and Non-Hodgkin's, who are eligible for a transplant. Participants should have CD30+ cancer cells, be over 3 years old, have good heart and lung function, and not be pregnant or breastfeeding. They must agree to use two forms of birth control if applicable.

Inclusion Criteria

Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent

I have recurrent Hodgkin lymphoma and will undergo high dose chemotherapy and possibly total body irradiation followed by autologous cell transplantation.

I have a specific type of lymphoma that is CD30+.

Exclusion Criteria

Received investigational agents or tumor vaccines within the previous six weeks prior to cell infusion

History of hypersensitivity reactions to murine protein-containing products

Pregnant or lactating

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Cell Procurement

Peripheral blood cells are collected for creation of ATLCAR.CD30 cells prior to ASCT

1-2 weeks

Up to 3 visits (in-person)

ASCT and Recovery

Patients undergo autologous stem cell transplantation and hematologic recovery

2-3 weeks

Inpatient stay

ATLCAR.CD30 Cells Administration

Administration of ATLCAR.CD30 cells post ASCT once hematologic recovery is achieved

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and survival of ATLCAR.CD30 cells

15 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• ATLCAR.CD30 cells

Trial Overview The study tests ATLCAR.CD30 cells in patients post-transplant to prevent relapse of lymphoma. These are T cells modified with a new gene making them better at recognizing and killing cancer cells by targeting the CD30 antigen found on some lymphoma cells.

How Is the Trial Designed?

Group I: ATLCAR.CD30 cells Experimental Treatment 1 Intervention

Three dose levels of ATLCAR.CD30 cells will be evaluated. Using the modified continual reassessment method (CRM), initial cohort of size two will be enrolled at each dose level after that subjects are enrolled one at a time until a minimum of 12 patients is treated. Each patient will receive one injection according to the dosing schedules listed below. Investigators will start with the lowest cell dose (2X10\^7 cells/m\^2) given to patients in one of our previous trials employing CAR-T cells including the CD28 costimulatory endodomain, and investigators will escalate the cell dose to the highest cell dose (2X10\^8/m\^2) given in the same trial. Note: Initially, only adults will be enrolled during the dose escalation phase of the study. Once a dose level has been tested in at least 2 adults without the occurrence of dose limiting toxicities (DLTs), children may then be enrolled on that dose level according to the CRM.

ATLCAR.CD30 cells is already approved in United States, European Union for the following indications:

Approved in United States as CD30 CAR-T cells for:

• Relapsed or refractory classical Hodgkin lymphoma

Approved in European Union as CD30 CAR-T cells for:

• Relapsed or refractory classical Hodgkin lymphoma

Who Is Running the Clinical Trial?

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

Trials

377

Recruited

95,900+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The combination of autologous stem-cell transplantation (ASCT) and CAR30 T-cell therapy was found to be safe and effective in treating relapsed/refractory CD30+ lymphoma, with 83.3% of patients achieving a complete response after treatment.

In a pilot study involving 6 patients, all of whom had previously poor prognoses, the treatment resulted in successful engraftment and maintained responses over a median follow-up of 20.4 months, indicating promising long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous stem cell transplantation in tandem with Anti-CD30 CAR T-cell infusion in relapsed/refractory CD30+ lymphoma. Zhang, P., Yang, X., Cao, Y., et al.[2022]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

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]

Third-generation anti-CD30 CAR T-cells (CD28BBz) show long-term persistence and strong anti-tumor activity in models of Hodgkin lymphoma and anaplastic large cell lymphoma, outperforming second-generation CAR T-cells (CD28z).

These CAR T-cells are well tolerated with minimal side effects, indicating they are a safe and effective treatment option for patients with Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The third-generation anti-CD30 CAR T-cells specifically homing to the tumor and mediating powerful antitumor activity. Zhang, S., Gu, C., Huang, L., et al.[2022]

In a study involving 41 heavily pretreated patients with relapsed or refractory Hodgkin lymphoma, CD30-targeted CAR T-cell therapy demonstrated a high overall response rate of 72%, with 59% achieving complete responses after fludarabine-based lymphodepletion.

The therapy showed a favorable safety profile, with most adverse events being grade 3 or higher hematologic issues and only mild cytokine release syndrome observed, indicating that CAR T-cell therapy can be safely extended to treat Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. Ramos, CA., Grover, NS., Beaven, AW., et al.[2022]

In a multi-center phase II clinical trial involving 12 patients with relapsed/refractory CD30+ lymphoma, the combination of anti-CD30 CAR-T therapy and PD-1 inhibitors resulted in a high overall response rate of 91.7%, with 50% of patients achieving complete remission.

The treatment demonstrated minimal toxicity, with only 4 patients experiencing cytokine release syndrome, and no cases of CAR-T-related encephalopathy syndrome, indicating a favorable safety profile alongside its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma. Sang, W., Wang, X., Geng, H., et al.[2022]

Chimeric antigen receptor (CAR)-transduced T cells targeting CD30 have shown to be safe and effective in treating Hodgkin lymphoma (HL).

The review also highlights the challenges and ongoing trials of using CAR-T cells targeting CD5 and CD7 in T-cell lymphomas (TCL), indicating a need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T Cells in Hodgkin and T-Cell Lymphomas. Muhsen, IN., Hill, LC., Ramos, CA.[2023]

The study demonstrates that CD30-targeted CAR-T cell therapy is effective in treating recurrent and malignant CD30-positive peripheral T-cell lymphomas (PTCL), showing significant tumor suppression in both laboratory and mouse model experiments.

The engineered 9C11-2 CAR T cells exhibited strong cytotoxic effects against CD30-positive cancer cells, indicating their potential as a promising therapeutic option for patients with this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new immunotherapy strategy targeted CD30 in peripheral T-cell lymphomas: CAR-modified T-cell therapy based on CD30 mAb. Wu, Y., Chen, D., Lu, Y., et al.[2022]

In a study of 38 classical Hodgkin's Lymphoma (cHL) specimens, only 5.2% of Reed-Sternberg cells expressed both CD19 and CD30, indicating a limited population eligible for combined CAR T-cell therapy.

A patient treated with low doses of anti-CD19 and CD30 CAR T-cells did not experience severe adverse events and achieved long-term progression-free survival, suggesting that this approach may be safe and effective for high-risk relapsing/refractory cHL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma. Xue, Y., Lai, X., Li, R., et al.[2022]

CAR-T cell therapy combined with anti-PD-1 immunotherapy shows promising efficacy in treating lymphoma, with an overall response rate of 65% based on an analysis of 57 patients from 5 clinical trials.

The most common adverse effect observed was fever, with a pooled incidence of 59%, indicating that while the therapy is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. Zhou, Y., Mu, W., Wang, C., et al.[2023]

CD30-directed CAR-T cells show promise as a treatment for relapsed or refractory lymphomas, particularly classical Hodgkin lymphoma, with early clinical trials indicating minimal toxicity and some preliminary efficacy.

Enhancing the persistence and expansion of CAR-T cells is crucial for improving treatment outcomes, with ongoing research focusing on optimizing treatment regimens and combining therapies to boost effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges of driving CD30-directed CAR-T cells to the clinic. Grover, NS., Savoldo, B.[2020]

CAR.λ T cells effectively target and kill Igλ+ lymphoma cells and chronic lymphocytic leukemia (CLL) cells, showing similar antitumor activity to the established CAR.CD19 T cells in both laboratory and animal models.

Importantly, CAR.λ and CAR.κ T cells selectively deplete only the corresponding light chain-expressing normal B cells, preserving the other type, which suggests a safer approach with minimal impact on the immune system's ability to produce antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells. Ranganathan, R., Shou, P., Ahn, S., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10394544/

Patient-reported outcomes in CD30-directed CAR-T cells ... We found an overall response rate of 62% in all evaluable patients. With a median follow-up of 533 days, the 1-year progression-free survival ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03602157

NCT03602157 | Study of CAR-T Cells Expressing CD30 ... Researchers are working to identify ways to improve the ability of ATLCAR.CD30 to destroy tumor cells. T cells naturally produce a protein called CCR4 which ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11731380/

Safety and efficacy of anti-CD30 CAR-T cell therapy in ... A total of 151 participants from 8 records were included. Meta-analysis showed the ORR of CD30 CAR-T cell therapy for R/R cHL was 57% (95%CI ...

4. nature.com nature.com/articles/s41598-022-14523-0

The third-generation anti-CD30 CAR T-cells specifically ... CAR T-cell therapy is well tolerated and effective in patients with Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL).

5. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3465/529134/Safety-and-Efficacy-of-CD30-Directed-Chimeric

Safety and Efficacy of CD30-Directed Chimeric Antigen ... The estimated 2-year overall survival (OS) was 100% and the median OS for all cHL patients has not been reached. Expansion and/or persistence of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02917083

Study Details | NCT02917083 | CD30 CAR T Cells, ... Genetic : CAR T Cells. Three dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three to six patients ...

7. med.unc.edu med.unc.edu/medicine/news/unc-hematology-and-lineberger-staff-published-a-study-on-anti-cd30-car-t-cell-therapy-in-high-risk-lymphoma-patients/

UNC Hematology and Lineberger Faculty Published a ... The study demonstrates the safety and promising activity of anti-CD30 CAR T cells as consolidation therapy after autologous haematopoietic ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-02015

Genetically Engineered Cells (ATLCAR.CD30.CCR4 CAR ... This phase Ib/II trial tests the safety, side effects, best dose and effectiveness of ATLCAR.CD30.CCR4 CAR T cells in treating patients with CD30 positive ...