MB-105 for T-cell Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: March Biosciences Inc
Must not be taking: CD5-targeted therapy, Systemic corticosteroids
Disqualifiers: Sezary syndrome, Active CNS lymphoma, others
No Placebo Group
Prior Safety Data
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.
12345Eligibility 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.
+7 more
Trial 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.
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Single armExperimental Treatment1 Intervention
This is a single arm, two-stage, Phase 2, open-label, multicenter study.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Baylor College of MedicineHouston, TX
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Who Is Running the Clinical Trial?
March Biosciences IncLead Sponsor
References
CAR T-Cells for the Treatment of Refractory or Relapsed Large B-Cell Lymphoma: A Single-Center Retrospective Canadian Study. [2023]Chimeric antigen receptor (CAR) T-cells are an important new third-line treatment option for large B-cell lymphoma (LBCL). The objective response rates in pivotal early phase clinical trials with CAR T-cells were very promising. The objective of this study was to describe the efficacy results obtained with CAR T-cells infusions in our institution and to compare the toxicities of our cohort with those of pivotal trials and studies conducted in a real-life setting.
FDA Approval Summary: Brexucabtagene Autoleucel for Treatment of Adults With Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. [2022]In October 2021, the FDA approved brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL). Approval was based on the phase II portion of ZUMA-3, a single-arm, open-label, multicenter trial that evaluated a single infusion of brexu-cel, preceded by lymphodepleting chemotherapy with cyclophosphamide and fludarabine, in this population. Efficacy was established on the basis of complete remission (CR) within 3 months after infusion and the duration of CR (DOCR). Among 54 patients in the efficacy analysis population, the CR rate was 52% (95% CI: 38, 66) with a median time-to-response of 56 days. With a median follow-up for responders of 7.1 months, the median DOCR was not reached. For all leukapheresed patients in the phase II portion of this trial (n = 71), the CR rate was 41% (95% CI: 29, 53). Among the 78 patients treated with the approved dose of brexu-cel, serious adverse reactions occurred in 79% and fatal adverse reactions occurred in 5% and included cerebral edema and infections. Cytokine release syndrome occurred in 92% (grade ≥3, 26%) and neurologic toxicities occurred in 87% (grade ≥3, 35%), leading to implementation of a risk evaluation and mitigation strategy (REMS). Postmarketing study with 15 years of follow-up will further evaluate long-term safety in adult patients with relapsed or refractory B-ALL.
Brexucabtagene autoleucel: a breakthrough in the treatment of mantle cell lymphoma. [2022]In July 2020, the U.S. Food and Drug Administration (FDA) approved brexucabtagene autoleucel (BA), the first anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for the treatment of relapsed/refractory mantle cell lymphoma (MCL). The pivotal ZUMA-2 trial led to the approval of BA in patients who experienced relapsed disease on prior therapies (chemotherapy and/or Bruton tyrosine kinase [BTK] inhibitors). The FDA approval of BA was based on excellent responses with this therapy in highly refractory patients with MCL, who conventionally had poor outcomes. Longer follow-up data from the ZUMA-2 study have been presented at recent international meetings. As is common with other CAR T-cell therapies in lymphomas, the main toxicities of BA therapy included cytokine release syndrome (CRS), infections, cytopenias and CAR-associated neurotoxicity. In this review, we provide a summary of the data in the development of BA and its impact on MCL patient survival and future directions.
Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.
CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]Patients with non-Hodgkin lymphomas (NHLs) resistant to standard therapies have a dismal prognosis. The outcome is even poorer in patients relapsing after autologous stem cell transplantation. Most of these patients do not qualify for an allogeneic hematopoietic cell transplantation (HCT) due to refractory disease, lack of a suitable allogeneic donor, higher age, or cumulative toxicity of previous chemotherapy. Despite patients undergoing allogeneic HCT normally profit from a graft-versus-lymphoma effect, overall survival in patients with NHL after HCT remains short. Therefore, novel treatment modalities are urgently needed. Chimeric antigen receptor (CAR)-T cells, a new class of cellular immunotherapy involving ex vivo genetic modification of T cells to incorporate an engineered CAR have been used in clinical trials. In the majority of studies, B cell malignancies treated with CD19 targeting CAR-T cells have been analyzed. Recently, results from 2 CD19 directed CAR-T cell trials with an increased follow-up of patients led to Food and Drug Administration and European Medicines Agency approval of tisagenlecleucel and axicabtagene ciloleucel. Common adverse events (AEs) include cytokine release syndrome and neurological toxicity, which may require admission to an intensive care unit, B cell aplasia and hemophagocytic lymphohistiocytosis. These AEs are manageable when treated by an appropriately trained team following established algorithm. In this review, we summarize the results of 3 large phase II CD19 CAR-T cell trials and focus on AEs. We also provide a perspective of ongoing activity in this field with the intend to improve the potency of this emerging novel therapy.