Cell Therapy for Non-Hodgkin's Lymphoma

Recruiting at 23 trial locations

Overseen By Harshita Gahankari

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Miltenyi Biomedicine GmbH

Must not be taking: Systemic corticosteroids

Disqualifiers: HIV, Active hepatitis B, Seizures, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

248 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new cell therapy called MB-CART2019.1 (also known as Zamtocabtagene autoleucel or Anti-CD20-anti-CD19 CAR T cells) for individuals with non-Hodgkin's lymphoma, a type of blood cancer. Researchers aim to assess the treatment's effectiveness and safety for those whose cancer has returned or hasn't responded to at least two prior treatments. The trial includes participants with specific types of this cancer, such as diffuse large B-cell lymphoma and mantle cell lymphoma, who have encountered difficulties with standard treatments. For those with persistent issues despite multiple treatments, this trial might be suitable. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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, it mentions that at least 2 weeks or 5 half-lives must have passed since your last systemic therapy before a certain procedure, so it's best to discuss your specific medications with the trial team.

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

Research has shown that MB-CART2019.1, a type of cell therapy, has been tested for safety in patients with relapsed or hard-to-treat non-Hodgkin's lymphoma. In earlier studies, most patients tolerated the treatment well, though some experienced common side effects like tiredness and fever.

An earlier study on safety revealed that some patients experienced more serious side effects, but medical care managed these effectively. As this trial progresses to a later stage, existing evidence supports the safety of MB-CART2019.1, although researchers continue to study the treatment to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, which often include chemotherapy and immunotherapy, MB-CART2019.1 is a type of cell therapy that uses modified T-cells to specifically target and attack cancer cells. Researchers are excited about this approach because it offers a more personalized treatment, potentially leading to better outcomes with fewer side effects. Additionally, the use of engineered T-cells aims to provide long-lasting protection by remaining active in the body to prevent recurrence.

What evidence suggests that this treatment might be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that zamtocabtagene autoleucel (MB-CART2019.1), the treatment under study in this trial, offers promise for individuals with relapsed or hard-to-treat diffuse large B cell lymphoma (DLBCL). This treatment employs CAR-T cells, which are specialized immune cells engineered to locate and destroy cancer cells. Studies have found that MB-CART2019.1 targets two proteins, CD19 and CD20, on the surface of cancerous B cells. This dual targeting likely enhances the treatment's effectiveness. Early results suggest that this approach can lead to a lasting response, potentially controlling the cancer for extended periods. ^{1 2 3 4 5}

Who Is on the Research Team?

Johanna Theruvath, MD

Principal Investigator

Miltenyi Biomedicine GmbH

Are You a Good Fit for This Trial?

Adults with Diffuse Large B-Cell Lymphoma (DLBCL) who have tried at least two other treatments without success can join this study. They should not be candidates for a stem cell transplant or must have chosen not to undergo one. Participants need to be over 18, in fairly good health otherwise, and able to follow birth control guidelines during the trial.

Inclusion Criteria

Platelet count > 50,000/μL

My condition did not improve after 2 chemotherapy treatments including rituximab and anthracycline, and I either can't have or chose not to have a stem cell transplant.

My total bilirubin level is below 1.5 mg/dl, unless I have Gilbert's syndrome.

Exclusion Criteria

I have an autoimmune disease affecting my nervous system.

Previous or concurrent malignancy with the following exceptions: Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry), In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study, Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years, A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years, History of non-neurologic autoimmune disease (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus)requiring systemic immunosuppressive or system disease modifying agents within the last 2 years, Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone >10 mg/day, History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment, Concurrent radiotherapy (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion). For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis, Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline, History of severe immediate hypersensitivity reaction to any of the agents used in this study, Refusal to participate in additional lentiviral gene therapy LTFU protocol, Prior CAR-T therapy for any indication or systemic gene modifying therapy for DLBCL, Prior allogeneic stem cell transplant for any indication, Prior BITE antibodies for cancer therapy, Prior T cell receptor-engineered T cell therapy

I have HIV or active hepatitis B, or I've treated hepatitis with undetectable viral load.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis and Lymphodepletion

Subjects undergo leukapheresis to collect cells for manufacturing and a lymphodepleting regimen with cyclophosphamide and fludarabine, or bendamustine in preparation for cell infusion

2-3 weeks

Treatment

Cell infusion administered intravenously at a dose of 2.5 x 10^6 CAR+ cells/kg body weight

1 day

Follow-up

Participants are monitored for efficacy and safety outcomes, as well as health-related quality of life (HRQoL) for up to 2 years

2 years

Long-term Follow-up

Additional long-term follow-up conducted under a separate protocol

What Are the Treatments Tested in This Trial?

Interventions

• MB-CART2019.1

Trial Overview The clinical trial is testing MB-CART2019.1 cells' effectiveness and safety in treating DLBCL that has resisted previous therapies. It's an open-label phase II study, meaning everyone gets the treatment and knows what it is, focusing on how well these cells work and their impact on patients.

How Is the Trial Designed?

Group I: Single, open label Experimental Treatment 4 Interventions

Who Is Running the Clinical Trial?

Miltenyi Biomedicine GmbH

Lead Sponsor

Trials

38

Recruited

1,700+

Published Research Related to This Trial

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]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

Adoptive cellular immunotherapy using anti-CD19 CAR-T cells has significantly improved treatment outcomes for patients with relapsed or refractory B cell lymphomas, leading to durable remissions, with two products already FDA-approved and a third in large clinical trials.

Despite their effectiveness, CAR-T cell therapies can cause serious side effects like infections and cytokine release syndrome, highlighting the need for better understanding of these toxicities and strategies to mitigate them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Kallam, A., Vose, JM.[2020]

CAR T-cell therapy targeting CD19 has transformed the treatment landscape for relapsed or refractory B-cell lymphomas, leading to rapid FDA approval for multiple lymphoma subtypes due to high response rates and durability.

Three second-generation anti-CD19 CAR T-cell products have been approved for use in aggressive non-Hodgkin's lymphoma, and ongoing research is focused on understanding treatment failures and improving outcomes for patients who do not respond to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphoma. Denlinger, N., Bond, D., Jaglowski, S.[2022]

CAR T-cell therapy, particularly with anti-CD19 targeting, has shown significant effectiveness in treating aggressive B-cell non-Hodgkin's lymphoma (NHL), leading to long-term remissions in patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to other treatments.

Two CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for refractory DLBCL, while a third product, liso-cel, is showing promising results in ongoing trials, although potential side effects like cytokine-release syndrome and neurotoxicity are important considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Chavez, JC., Bachmeier, C., Kharfan-Dabaja, MA.[2020]

CAR-T cell therapy targeting the CD19 antigen has significantly changed treatment for patients with relapsed or refractory B cell non-Hodgkin lymphoma, with two FDA-approved products available: axicabtagene ciloleucel and tisagenlecleucel.

The review highlights the clinical outcomes and toxicity profiles of these CAR-T therapies, indicating their effectiveness across major B cell NHL subtypes, while also discussing new CAR-T constructs currently being researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor modified T cell therapy in B cell non-Hodgkin lymphomas. Levin, A., Shah, NN.[2021]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

Chimeric-antigen-receptor T cells (CAR-T) targeting CD19 are associated with several adverse drug reactions (ADRs), with the most common being cytokine release syndrome (CRS), neurological disorders, and hematological disorders, as identified in a study analyzing 1783 safety reports.

While CAR-T therapy can lead to severe ADRs, particularly in the week following administration, the overall fatality rate from these reactions is relatively low at 5.5%, though serious conditions like hemophagocytic-lymphohistiocytosis and infections require careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells safety: A pharmacovigilance and meta-analysis study. Dolladille, C., Ederhy, S., Ezine, E., et al.[2021]

A 61-year-old male with relapsed diffuse large B-cell lymphoma achieved significant therapeutic success and has been disease-free for over 12 months after receiving CAR-T cell therapy combined with a PD-1 inhibitor, highlighting the potential of this combination treatment.

The patient's T cell function was enhanced by the PD-1 inhibitor prior to CAR-T cell infusion, suggesting that targeting immune checkpoints can improve the efficacy of CAR-T therapy in patients with refractory lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed cell death protein-1 inhibitor combined with chimeric antigen receptor T cells in the treatment of relapsed refractory non-Hodgkin lymphoma: A case report. Niu, ZY., Sun, L., Wen, SP., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04792489

NCT04792489 | DALY II USA/ MB-CART2019.1 for DLBCL DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel ...

2. emjreviews.com emjreviews.com/hematology/abstract/zamtocabtagene-autoleucel-mb-cart2019-1-an-investigational-car-t-cell-product-with-tandem-targeting-of-cd19-and-cd20-as-a-potential-treatment-option-for-patients-with-relapsed-refractory-b-cell-no-j06/

Zamtocabtagene Autoleucel (MB-CART2019.1) An investigational CAR-T cell product with tandem targeting of CD19 and CD20 as a potential treatment option for patients with relapsed/refractory B cell non- ...

3. researchgate.net researchgate.net/publication/368580872_Zamtocabtagene_Autoleucel_MB-CART20191_An_Investigational_CAR-T_Cell_Product_with_Tandem_Targeting_of_CD19_and_CD20_as_a_Potential_Treatment_Option_for_Patients_with_Relapsed_Refractory_B_Cell_Non-Hod

Zamtocabtagene Autoleucel (MB-CART2019.1) A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma. February 2022 · Chinese Journal of Cancer ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9431345/

PHASE I TRIAL OF MB-CART2019.1 IN PATIENTES WITH ... Aims: This first-in-human, Phase I study had the objective to assess feasibility, safety and toxicity of ex vivo generated MB-CART2019.1 in mainly elderly ...

5. miltenyibiomedicine.com miltenyibiomedicine.com/DALY1_2022_EHA.pdf

phase i trial of mb-cart2019.1 in patients with relapsed or ... safety of MB-CART2019.1 in patients with relapsed or refractory (r/r) CD20 and. CD19 positive B cell non-Hodgkin lymphoma (B-NHL). Here, we report the results.