Cell Therapy for Non-Hodgkin's Lymphoma

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

8 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Rituximab for treating non-Hodgkin's lymphoma?

Rituximab has been shown to significantly improve outcomes in both aggressive and slow-growing forms of non-Hodgkin's lymphoma, achieving high response rates when combined with chemotherapy. It was the first targeted therapy for lymphoma and has been widely adopted for its effectiveness. ^{1 2 3 4 5}

Is rituximab generally safe for humans?

Rituximab is generally well tolerated, but some patients may experience side effects like infusion reactions, which can be serious in rare cases. Common side effects include fever and chills during the first infusion, and there are rare reports of heart-related issues like high blood pressure and heart attacks. ^{6 7 8 9 10}

How is the drug Rituximab unique in treating non-Hodgkin's lymphoma?

Rituximab is unique because it was the first targeted therapy developed for lymphoma, specifically targeting the CD20 protein on B-cells, and it has significantly improved outcomes for patients with both aggressive and indolent forms of non-Hodgkin's lymphoma. ^{1 2 4 5 11}

What is the purpose of this trial?

This phase I/II trial studies the side effects and best dose of genetically engineered lymphocyte therapy and to see how well it works after peripheral blood stem cell transplant (PBSCT) in treating patients with high-risk, intermediate-grade, B-cell non-Hodgkin lymphoma (NHL). Genetically engineered lymphocyte therapy may stimulate the immune system in different ways and stop cancer cells from growing. Giving rituximab together with chemotherapy before a PBSCT stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim (G-CSF), or plerixafor helps stem cells move from the bone marrow to the blood so they can be collected and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving genetically engineered lymphocyte therapy after PBSCT may be an effective treatment for NHL.

Research Team

Elizabeth L Budde, MD,PhD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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]

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 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]

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]

References

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

Rituximab therapy of B-cell neoplasms. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Clinical Efficiency of Rituximab Combined with Autologous Hematopoietic Blood Stem Cell Transplantation for Treatment of CD20+ B non.Hodgkin Lymphoma]. [2021]

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

Effects of pretransplantation treatment with rituximab on outcomes of autologous stem-cell transplantation for non-Hodgkin's lymphoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Anterior ST-elevation myocardial infarction induced by rituximab infusion: A case report and review of the literature. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? [2021]

8. England pubmed.ncbi.nlm.nih.gov

Improved survival in HIV-associated diffuse large B-cell lymphoma with the addition of rituximab to chemotherapy in patients receiving highly active antiretroviral therapy. [2015]

9. United States 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. [2022]

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

Use of rituximab, the new FDA-approved antibody. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. [2022]