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

Trial Summary

What is the purpose of this trial?

This is a single arm, two-stage, Phase 2, open-label, multicenter study of MB-105 in patients with CD5 Positive (CD5+) Relapsed / Refractory T-cell Lymphoma (r/r TCL). This study will apply a Simon two-stage optimal design.

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.

What safety data exists for MB-105 or similar CAR T-cell therapies?

CAR T-cell therapies, like MB-105, have been studied for various conditions and generally show some common safety concerns. These include cytokine release syndrome (a severe immune reaction) and neurological toxicities, which can be serious but are manageable with proper medical care. Some studies report no serious adverse events directly linked to the treatment, indicating a potentially good safety profile in certain settings. ^{1 2 3 4 5}

Research Team

Alice Bexon, MD, CMO

Principal Investigator

March Bio

Eligibility Criteria

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

I am 18 years old or older.

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.

Timeline

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.

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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]

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]

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]

References

1. United States 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. [2023]

2. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Brexucabtagene Autoleucel for Treatment of Adults With Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

Brexucabtagene autoleucel: a breakthrough in the treatment of mantle cell lymphoma. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]