MB-105 for T-cell Lymphoma

Recruiting at 11 trial locations

Overseen By Federica Giordano, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: March Biosciences Inc

Must not be taking: CD5-targeted therapy, Systemic corticosteroids

Disqualifiers: Sezary syndrome, Active CNS lymphoma, 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

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called MB-105 for individuals with T-cell lymphoma that has returned or not responded to previous treatments. The goal is to evaluate the effectiveness of MB-105 in patients whose cancer cells display a specific marker called CD5. Suitable candidates include those with relapsed or refractory T-cell lymphoma who have not benefited from standard treatments and have tumors testing positive for CD5. As a Phase 2 trial, the research focuses on assessing 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 must stop taking your current medications. However, if you are on systemic corticosteroids at a dose higher than 10 mg/day of prednisone (or equivalent), a 2-week period without these medications is required before certain procedures in the trial.

Is there any evidence suggesting that MB-105 is likely to be safe for humans?

Research has shown that MB-105 was safe in earlier studies. The Independent Data Monitoring Committee (IDMC), responsible for safety oversight, has not approved any dose higher than those deemed safe in these studies. Therefore, the doses currently tested should be manageable for participants.

Earlier trials established strict eligibility criteria, such as requiring good organ function and avoiding certain treatments in close succession. These measures ensure MB-105 is tested on individuals likely to tolerate it well.

In summary, MB-105 demonstrated safety in previous tests, and researchers are proceeding cautiously in current trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

MB-105 is unique because it targets T-cell lymphoma by enhancing the body's immune response. Unlike traditional chemotherapy treatments, which attack both cancerous and healthy cells, MB-105 is designed to specifically hone in on and eliminate lymphoma cells, reducing collateral damage to healthy cells. Researchers are particularly excited about its potential to improve outcomes with fewer side effects, offering a more targeted and efficient approach to cancer treatment.

What evidence suggests that MB-105 might be an effective treatment for T-cell Lymphoma?

Research has shown that MB-105 yields promising results for treating CD5 Positive Relapsed/Refractory T-cell Lymphoma. In earlier studies, 44% of patients experienced a reduction or disappearance of their cancer, with some achieving complete remission, meaning no signs of cancer were found. These findings suggest that MB-105 could be effective for this difficult-to-treat cancer. The treatment has also received Orphan Drug Designation, indicating its potential for treating rare diseases like this one. Participants in this trial will receive MB-105 in a single-arm study to further evaluate its effectiveness. ^{2 3 6 7 8}

Who Is on the Research Team?

Alice Bexon, MD, CMO

Principal Investigator

March Bio

Are You a Good Fit for This Trial?

This trial is for adults over 18 with CD5 Positive T-cell Lymphoma that's come back or hasn't responded to treatment. They should have tried at least one or two standard treatments, depending on the type of lymphoma. Participants need a performance score showing they're fairly active and must have measurable disease. Those who've had CAR T-cell therapy can join if it was over 60 days ago and there are no remaining CAR cells.

Inclusion Criteria

My condition is relapsed or refractory T-cell lymphoma as per WHO 2022.

I can provide a sample of my tumor or am willing to have a biopsy.

My cancer cells tested positive for CD5.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Stage 1

Stage 1 involves dosing of MB-105 and safety analysis by IDMC after the first 6 patients, followed by enrollment of additional 9 patients to complete 15 total.

8 weeks

Multiple visits for dosing and safety assessments

Treatment - Stage 2

Stage 2 involves enrollment of approximately 31 additional patients, with ongoing safety and efficacy reviews by IDMC.

6 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with a minimum follow-up of 12 months.

12 months

Regular follow-up visits

Long-term Follow-up

Participants are asked to participate in a separate long-term follow-up study after the end of study visit.

What Are the Treatments Tested in This Trial?

Interventions

• MB-105

Trial Overview The study tests MB-105, a genetic intervention, in patients with relapsed/refractory T-cell Lymphoma. It's an open-label Phase 2 trial using a Simon two-stage optimal design, meaning researchers will assess results at two points to decide if they should continue.

How Is the Trial Designed?

Group I: Single arm Experimental Treatment 1 Intervention

This is a single arm, two-stage, Phase 2, open-label, multicenter study.

Who Is Running the Clinical Trial?

March Biosciences Inc

Lead Sponsor

Trials

1

Recruited

50+

Published Research Related to This Trial

In a study of 25 patients with large B-cell lymphoma treated with CAR T-cell therapy, the objective response rates were 20% for tisagenlecleucel and 47% for axicabtagene-ciloleucel at 3 months, indicating variable efficacy based on the type of CAR T-cell used.

Bulky disease was identified as a significant negative predictor of response, with patients having bulky disease showing a median progression-free survival of only 2 months compared to 5 months for those without bulky disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study. Benoit, A., B Boies, MH., Déry, N., et al.[2023]

Brexucabtagene autoleucel (BA) is the first FDA-approved CAR T-cell therapy specifically for relapsed/refractory mantle cell lymphoma (MCL), showing excellent response rates in patients who had poor outcomes with previous treatments.

While BA therapy demonstrated significant efficacy, it is associated with common toxicities such as cytokine release syndrome, infections, and neurotoxicity, which are typical for CAR T-cell therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexucabtagene autoleucel: a breakthrough in the treatment of mantle cell lymphoma. Deshpande, A., Wang, Y., Munoz, J., et al.[2022]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

Brexucabtagene autoleucel (brexu-cel) is an FDA-approved CAR T-cell therapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL), showing a complete remission (CR) rate of 52% within 3 months after treatment in a study of 54 patients.

While brexu-cel demonstrates significant efficacy, it is associated with serious adverse reactions in 79% of patients, including severe cytokine release syndrome (92%) and neurological toxicities (87%), necessitating a risk evaluation and mitigation strategy (REMS) for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Brexucabtagene Autoleucel for Treatment of Adults With Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Bouchkouj, N., Lin, X., Wang, X., et al.[2022]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS7086

A phase 2 study to confirm safety and efficacy of MB-105 ... In the phase 1 trial, 44% (4/9) patients experienced objective responses, including 2/3 complete responses with survival >5 years. Mid-trial ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06534060

MB-105 in Patients With CD5 Positive T-cell Lymphoma The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

3. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/march-biosciences-mb-105-dosed-in-first-t-cell-lymphoma-patient/

March Biosciences MB-105 Dosed in First T-Cell ... The Phase 2 trial is a multi-center, open-label study. Phase 1 results showed a 93% manufacturing success rate for CD5 CAR-T cells and no high- ...

4. onclive.com onclive.com/view/mb-105-receives-orphan-drug-designation-in-relapsed-refractory-cd5-t-cell-lymphoma

MB-105 Receives Orphan Drug Designation in Relapsed ... MB-105 has shown a 44% overall response rate in relapsed/refractory T-cell lymphoma, with two complete responses in the phase 1 MAGENTA trial.

5. targetedonc.com targetedonc.com/view/fda-grants-orphan-drug-designation-to-mb-105-for-r-r-t-cell-lymphoma

FDA Grants Orphan Drug Designation to MB-105 for R/R T- ... Preliminary results from the study suggest the agent elicits a 44% overall response rate among those with T-cell lymphoma.

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7223/528290/Confirmatory-Efficacy-and-Safety-Evaluation-of-MB

Confirmatory Efficacy and Safety Evaluation of MB-105, a CD5 ... We designed this study to confirm efficacy and safety of MB-105 in a multicenter setting across the United States in patients with R/R peripheral TCL (PTCL) or ...

7. clinicaltrials.uihealthcare.org clinicaltrials.uihealthcare.org/studies/phase-2-open-label-multicenter-study-mb-105-patients-cd5-positive-cd5-relapsed-refractory-t

A phase 2, open-label, multicenter study of MB-105 in patients ... The IDMC will not recommend a MB-105 dose greater than those found safe in the phase 1 study. During the safety analysis period after the 6th patient is treated ...

8. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT06534060

MB-105 in Patients With CD5 Positive T-cell Lymphoma The IDMC will not recommend a MB-105 dose greater than those found safe in the phase 1 study. During the safety analysis period after the 6th ...