Cell Therapy for Non-Hodgkin's Lymphoma

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: City of Hope Medical Center

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: HIV, Autoimmune disease, Hepatitis, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for high-risk B-cell non-Hodgkin's lymphoma using genetically engineered lymphocytes, special immune cells designed to target cancer. The trial aims to determine the optimal dose and assess any side effects, particularly after a stem cell transplant. Participants will receive rituximab (an antibody therapy) and chemotherapy before the transplant to help control cancer cells. This trial may suit those who have relapsed or did not achieve remission with initial treatment and require a stem cell transplant. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are dependent on corticosteroids or require systemic immunosuppressive therapy for an active autoimmune disease, you may not be eligible to participate.

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

Research has shown that treatments like CAR-T cell therapy, which use specially modified immune cells, might be safe and manageable for people with non-Hodgkin lymphoma (NHL). Studies have found that these therapies can work for patients who did not respond to other treatments. For instance, one study on CAR-T cells for a similar type of NHL found that while patients could handle the treatment, they experienced some side effects.

Early-phase trials like this one focus on understanding the treatment's safety. Since this trial is in phases 1 and 2, researchers are still learning about possible side effects. This stage is crucial to ensure the treatment's safety before testing it on more people. While there is hope for the therapy's benefits, anyone considering participation should know that the full range of side effects and long-term safety is still under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment because it employs cellular adoptive immunotherapy, which is a novel approach compared to standard treatments like chemotherapy and monoclonal antibodies. Most treatments for Non-Hodgkin's Lymphoma, such as rituximab, work by targeting cancer cells directly. In contrast, this therapy enhances the patient's immune response by using T cells engineered to express a CD19-specific CAR, which boosts their ability to recognize and attack lymphoma cells. This could potentially lead to a more effective and sustained treatment response, offering hope for improved outcomes in patients with this condition.

What evidence suggests that genetically engineered lymphocyte therapy might be an effective treatment for non-Hodgkin's lymphoma?

Earlier studies have shown that CD19-specific CAR-T cell therapy successfully treats B-cell non-Hodgkin lymphoma (NHL). This therapy targets the CD19 marker found on most B-cell NHLs. Research indicates that CAR-T cell treatments can extend patient survival, with one study showing about 30% of patients experienced no cancer events for five years. In this trial, participants will receive cellular adoptive immunotherapy following PBSCT, which includes the infusion of ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR. Although there is a risk of cancer returning, these therapies represent a significant advancement in treating high-risk B-cell NHL. ^{1 2 4 6 7}

Who Is on the Research Team?

Elizabeth L Budde, MD,PhD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with high-risk B-cell non-Hodgkin lymphoma who've had a relapse or didn't respond to initial treatment. They must be fit enough for stem cell transplant (Karnofsky score ≥70%), not pregnant, and have a life expectancy over 16 weeks. Excluded are those with HIV, prior transplants, active autoimmune diseases needing steroids, hepatitis B/C infection, or on other trials.

Inclusion Criteria

My cancer returned after initial treatment or didn't respond to the first treatment.

I am able to care for myself but may not be able to do active work.

I am eligible for a stem cell transplant using my own cells.

Exclusion Criteria

I rely on corticosteroids for my health condition.

I have an active hepatitis B or C infection.

I don't have any health issues that would prevent me from undergoing a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy and Stem Cell Mobilization

Patients receive standard salvage chemotherapy and undergo mobilization for stem cell collection with filgrastim and/or plerixafor. Some may receive rituximab IV within 4 weeks of transplant.

4 weeks

Conditioning and Transplantation

Patients receive standard myeloablative conditioning followed by autologous PBSCT.

1 week

Cellular Immunotherapy

Infusion of ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR on day 2 or 3 after transplant.

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for dose limiting toxicities and engraftment.

28 days

Long-term Follow-up

Patients are followed up periodically for at least 15 years to assess long-term outcomes such as progression-free survival.

15 years

What Are the Treatments Tested in This Trial?

Interventions

• Filgrastim
• Genetically Engineered Lymphocyte Therapy
• Plerixafor
• Rituximab

Trial Overview The study tests genetically engineered lymphocyte therapy after stem cell transplant in patients with aggressive lymphoma. It includes rituximab and chemotherapy before the transplant and factors like filgrastim to help move stem cells from bone marrow into the blood for collection.

How Is the Trial Designed?

Group I: Treatment (cellular adoptive immunotherapy following PBSCT) Experimental Treatment 7 Interventions

Patients receive standard salvage chemotherapy per standard practice and undergo standard mobilization for stem cell collection with G-CSF and/or plerixafor. Some patients may also receive rituximab IV within 4 weeks of transplant. Patients receive standard myeloablative conditioning followed by autologous PBSCT. Patients then undergo infusion of ex vivo expanded autologous TCM-enriched CD8+ T cells expressing CD19-specific CAR on day 2 or 3 after transplant.

Rituximab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in European Union as MabThera for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Approved in Canada as Rituxan for:

• Non-Hodgkin's lymphoma
• Chronic lymphocytic leukemia
• Rheumatoid arthritis
• Granulomatosis with polyangiitis
• Microscopic polyangiitis

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Rituximab has significantly improved survival rates in patients with non-Hodgkin lymphomas, but there is a lack of comprehensive data on its long-term safety, indicating a need for extended patient follow-up.

Current literature provides limited guidance on systematic follow-up models for patients receiving rituximab, highlighting the necessity for developing monitoring strategies to ensure patient safety and optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? Hegele, V., Stoll, P., Wüst, D., et al.[2021]

In a study of 33 patients with aggressive non-Hodgkin's lymphoma, the combination of Rituxan (rituximab) and CHOP chemotherapy resulted in a high overall response rate of 94%, with 61% achieving a complete response.

The treatment was well-tolerated, with common side effects like fever and chills, and did not hinder the completion of the full six-course regimen, indicating both safety and efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of rituximab in combination with chop chemotherapy in patients with previously untreated, aggressive non-Hodgkin's lymphoma. Vose, JM., Link, BK., Grossbard, ML., et al.[2022]

Rituximab was the first monoclonal antibody approved for cancer therapy and has significantly improved survival rates in patients with diffuse large cell lymphoma when combined with CHOP chemotherapy.

Initially approved in 1997 for relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma, rituximab is also being researched for other B-cell malignancies and nonmalignant diseases like autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. King, KM., Younes, A.[2015]

Rituximab is the first FDA-approved monoclonal antibody for cancer treatment, specifically targeting the CD20 antigen on B cells, and has shown efficacy in treating relapsed low-grade and follicular non-Hodgkin's lymphoma in multicenter studies.

The treatment is generally well-tolerated, with side effects mainly consisting of mild fevers and chills during the first infusion, and its low immunogenicity allows for potential future treatments without significant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. Leget, GA., Czuczman, MS.[2019]

Rituximab has significantly improved outcomes for patients with Non-Hodgkin's lymphoma (NHL), particularly in aggressive forms like diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL).

The treatment is generally well-tolerated by patients and has been shown to be cost-effective, making it a valuable option in both initial and relapsed cases of B cell NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in the treatment of non-Hodgkin's lymphoma--a critical evaluation of randomized controlled trials. Griffin, MM., Morley, N.[2020]

Rituximab, a monoclonal antibody used for treating certain cancers and autoimmune diseases, is generally well tolerated but can cause serious side effects, including rare but life-threatening cardiovascular events like myocardial infarction.

A case study of a 58-year-old man revealed that he experienced a ST-elevation myocardial infarction during rituximab treatment, highlighting the need for careful screening for ischemic heart disease in patients receiving this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature. Sharif, K., Watad, A., Bragazzi, NL., et al.[2022]

In a phase II study involving 37 patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, Rituximab was found to be well tolerated, with most adverse events being mild and decreasing with subsequent infusions.

The treatment resulted in a 57% overall response rate, with 14% achieving a complete response and 43% a partial response, indicating significant clinical activity and suggesting that extended Rituximab treatment may be effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Piro, LD., White, CA., Grillo-López, AJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8261235/

A Deep Insight Into CAR-T Cell Therapy in Non-Hodgkin ... CD19-specific CAR-T cells have been widely used to treat B-cell lymphoma since most B-cell NHLs also highly express the CD19 marker. However, the clinical ...

2. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).

3. ashpublications.org ashpublications.org/bloodadvances/article/9/20/5362/546293/Survival-after-anti-CD19-CAR-T-cell-therapy-for-B

Survival after anti-CD19 CAR T-cell therapy for B-cell non ... Previous publication of 5-year follow-up data of axi-cel for LBCL demonstrated an estimated 5-year event-free survival (EFS) of 30.3% and overall survival (OS) ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725012618

Real-World Treatment Patterns and Out-of-Pocket Costs ... Clinical trial data indicate relapse rates up to 50% within 6 months, but real-world evidence on salvage therapy patterns and financial burdens is limited.

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2022/nhl-car-t-cells-belinda-transform-zuma7

CAR T Cells: Second-Line Treatment Option for NHL? - NCI New results from three large clinical trials now suggest that, after initial chemotherapy, CAR T-cell therapies may be more effective than standard treatment.

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-10266

Genetically Engineered Cells (TmCD19-IL18 CAR T ... TmCD19-IL18 CAR T cells may be safe, tolerable and/or effective in treating patients with CD19+ relapsed or refractory non-Hodgkin lymphoma. Eligibility ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05418088

NCT05418088 | Genetically Engineered Cells (Anti-CD19/ ... This phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19/CD20/CD22 chimeric antigen ...