Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Sana Biotechnology
No Placebo Group
Trial Summary
What is the purpose of this trial?SC262-101 is a Phase 1 study to evaluate SC262 safety and tolerability, anti-tumor activity, cellular kinetics, immunogenicity, and exploratory biomarkers.
What safety data is available for SC262 treatment in Non-Hodgkin's Lymphoma?The safety data for SC262, a CAR T-cell therapy, includes information on common side effects such as cytokine release syndrome (CRS), neurological events (NE), prolonged cytopenias, and hypogammaglobulinemia. Studies have shown that most patients recover from these side effects. Additionally, a low incidence of invasive fungal disease (IFD) was observed, with early toxicities like CRS (85%) and ICANS (55%) being common. Late toxicities included grades 3 and 4 neutropenia (41%) and low CD4 T-cell count (20%). Overall, CAR T-cell therapy has shown high safety and efficacy in treating relapsed/refractory B-cell lymphoma.89101112
What data supports the idea that SC262 for Non-Hodgkin's Lymphoma is an effective treatment?The available research does not provide specific data on SC262 for Non-Hodgkin's Lymphoma. However, it mentions that complete remission can be achieved in 50 to 80% of patients with high-grade non-Hodgkin's lymphoma using standard treatments like CHOP. For refractory cases, the SCHOLAR-1 study shows poor outcomes with other treatments, indicating a need for more effective options. Without specific data on SC262, it's unclear how it compares to these existing treatments.4571314
Is the drug SC262 a promising treatment for Non-Hodgkin's Lymphoma?Yes, SC262 is a promising drug for Non-Hodgkin's Lymphoma because treatments for this disease have been improving, and many patients achieve complete remission, meaning the cancer is no longer detectable. This suggests that new treatments like SC262 could be effective.12346
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or corticosteroids (more than 10 mg/day prednisone or equivalent), you may not be eligible to participate.
Eligibility Criteria
This trial is for adults aged 18-80 with certain B-cell malignancies, including various types of non-Hodgkin's lymphoma and mantle cell lymphoma. Participants must have relapsed or refractory disease after no more than one prior therapy, a life expectancy of at least 12 weeks, and be physically capable (ECOG status 0-1).Inclusion Criteria
Histologic diagnosis of NHL (based on World Health Organization 2016 criteria) including: LBCL, including Diffuse Large B Cell Lymphoma (DLBCL) not otherwise specified (NOS) (including DLBCL arising from indolent lymphoma), Primary Mediastinal Large B-Cell Lymphoma (PMBCL), High-Grade B-Cell Lymphoma (HGBCL), and Follicular Lymphoma (FL) Grade 3B, FL, Marginal Zone Lymphomas (MZL), Mantle Cell Lymphoma (MCL), Relapsed or refractory disease after no more than 1 prior CD19-directed CAR T cell therapy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, At least 1 measurable (PET-positive) lesion per Lugano classification, Life expectancy ≥12 Weeks
I am between 18 and 80 years old.
Treatment Details
The study is testing SC262, a new treatment for B-cell malignancies. It's in Phase 1 to check its safety, how well it works against cancer cells, what the body does to it over time, if it causes immune reactions and to look at some early signs that might predict who benefits.
1Treatment groups
Experimental Treatment
Group I: SC262 Plus Chemotherapy RegimenExperimental Treatment1 Intervention
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment with SC262
Find a clinic near you
Research locations nearbySelect from list below to view details:
Swedish Cancer InstituteSeattle, WA
The University of Kansas HospitalKansas City, KS
Fred Hutchinson Cancer CenterSeattle, WA
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Who is running the clinical trial?
Sana BiotechnologyLead Sponsor
References
Recent advances in the management of non-Hodgkin's lymphomas. [2006]The non-Hodgkin's lymphomas are a diverse group of diseases with distinctive natural histories and responsiveness to therapy. Each of these diseases represents the arrest and proliferation of malignant lymphocytes at a particular stage of normal lymphocyte differentiation. Cytogenetic and gene rearrangement studies have established the clonal nature of these disorders. The majority of the non-Hodgkin's lymphomas that occur in adults are of B cell origin. Exceptions to this are lymphoblastic lymphoma, mycosis fungoides, Sézary syndrome, and HTLV-1 associated leukemia--lymphomas that are diseases of T cell origin. As a group, the non-Hodgkin's lymphomas are diseases that are very responsive to radiation therapy and chemotherapy. There are major differences, however, in the durability of these responses. From a clinical standpoint, the non-Hodgkin's lymphomas may be divided into those that are indolent and those that are aggressive in their clinical behavior. Ironically, the aggressive non-Hodgkin's lymphomas are frequently curable, while the indolent non-Hodgkin's lymphomas are presently incurable in the majority of cases.
Non-Hodgkin's lymphomas. [2019]The non-Hodgkin's lymphomas are a group of diseases for which substantial progress has been made in understanding tumor biology and effectiveness of treatment during the last few years. These advances may provide insight into the development of neoplasms because of recognized association of lymphomas with viral infections and immunodeficiency. The prognosis for patients with non-Hodgkin's lymphomas continues to improve. As a result, current studies on treatment of lymphomas in certain favorable stages have concentrated on reducing the intensity of therapy. For patients with advanced disease, further improvements in treatment are being sought.
Follicular (nodular) lymphoma during the first two decades of life: a clinicopathologic study of 12 patients. [2021]Twelve patients who developed non-Hodgkin's lymphoma with a follicular pattern during the first two decades of life were studied. Eight had the poorly differentiated lymphocytic type; the remaining four had the "histiocytic" type. Eleven of the 12 patients were male. Nine were asymptomatic, and eight had lymphadenopathy in the head and neck region. Comparison of ages revealed the extent of disease tended to be localized (Stages I and II) in the pediatric (less than 16 years old) patients (83%) and generalized in the adolescent-young adult (16-19 years old) patients (83%). Of ten patients treated with chemotherapy and/or radiotherapy, eight achieved complete remissions that lasted 3-58 months (median, 17.5 months). Five are still in remission; three have relapsed. Seven are alive 12-120 months from diagnosis (median, 48 months); six have no clinical evidence of disease. The remaining five patients died two to 164 months after diagnosis (median, 13 months). Three of the four patients who died with lymphoma had diffuse "histiocytic" lymphoma demonstrated at autopsy examination. Poor prognostic factors included 1) failure to achieve a complete remission following initial therapy; 2) extranodal disease (with the exception of the poorly differentiated lymphocytic type involving the spleen and liver); 3) development of diffuse "histiocytic" lymphoma. Follicular lymphoma occurring in the second decade of life has a biologic behavior similar to follicular lymphoma in adults.
[Therapy of high-grade non-Hodgkin's lymphoma]. [2015]Complete remission can be achieved in 50 to 80% of adult patients with high-grade non-Hodgkin's lymphoma [2, 33]. The average disease-free survival is 40 to 50% at 3 years and 30 to 35% at 5 years [2, 6]. The diagnosis of non-Hodgkin's lymphoma should still be based on the histopathological and immunohistochemical evaluation of a surgical biopsy specimen. Initial staging involves radiological evaluation of tumor mass and lymph-node involvement, bone marrow biopsy, conventional laboratory investigations including LDH and beta 2-microglobulin, as well as chromosome analysis and molecular biology. These methods are also used for monitoring of patients during and after therapy. Established negative risk factors include age over 60 years, clinical stage III or IV, involvement of more than 1 extranodal site, a WHO performance status of 2 or more, and an elevation of the LDH. CHOP remains the standard chemotherapy. Aggressive regimens of the second and third generations, as well as dose-intensification have failed to prove a superior effect on overall survival [7]. Full-dose treatment on schedule can be facilitated by supportive therapy with cytokines such as G-CSF or GM-CSG. High-risk patients may have a favorable outcome after myeloablative chemotherapy and radiation followed by autologous or allogeneic bone marrow transplantation. Co-ordinated planning between conventional centers and transplant units should lead to a risk adjusted treatment of the individual patient.
Lymphoma 2006: classification and treatment. [2006]The past 20 years have brought significant advances in our ability to manage patients with non-Hodgkin's lymphoma. More precise classification systems, improvements in diagnosis and staging, and effective new treatments have improved outcomes and made cure a reasonable goal for many patients with these disorders. In this overview of the progress seen in the field over the past 2 decades, we describe a variety of advances for specific lymphomas, including diagnostic methods such as gene array studies and immunophenotyping and new treatment approaches.
Lack of efficacy of imiquimod in patients with basal cell carcinoma previously treated with rituximab for B cell lymphoma: two case reports. [2018]Non-Hodgkin lymphomas are a heterogeneous group, which involve either B or T lymphocytes. The most used treatment is a chemotherapy regimen, which includes cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone combined with rituximab - a monoclonal antibody specific for CD20 - an antigen expressed on B lymphocyte membrane. Nonmelanoma skin cancers are the most common forms in patients who have lymphomas.
Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. [2022]Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Although 5-year survival rates in the first-line setting range from 60% to 70%, up to 50% of patients become refractory to or relapse after treatment. Published analyses of large-scale outcome data from patients with refractory DLBCL are limited. SCHOLAR-1, an international, multicohort retrospective non-Hodgkin lymphoma research study, retrospectively evaluated outcomes in patients with refractory DLBCL which, for this study, was defined as progressive disease or stable disease as best response at any point during chemotherapy (>4 cycles of first-line or 2 cycles of later-line therapy) or relapsed at ≤12 months from autologous stem cell transplantation. SCHOLAR-1 pooled data from 2 phase 3 clinical trials (Lymphoma Academic Research Organization-CORAL and Canadian Cancer Trials Group LY.12) and 2 observational cohorts (MD Anderson Cancer Center and University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence). Response rates and overall survival were estimated from the time of initiation of salvage therapy for refractory disease. Among 861 patients, 636 were included on the basis of refractory disease inclusion criteria. For patients with refractory DLBCL, the objective response rate was 26% (complete response rate, 7%) to the next line of therapy, and the median overall survival was 6.3 months. Twenty percent of patients were alive at 2 years. Outcomes were consistently poor across patient subgroups and study cohorts. SCHOLAR-1 is the largest patient-level pooled retrospective analysis to characterize response rates and survival for a population of patients with refractory DLBCL.
Stomatitis And Everolimus: A Review Of Current Literature On 8,201 Patients. [2022]Oral toxicities, such as mucositis and stomatitis, are some of the most significant and unavoidable side effects associated with anticancer therapies. In past decades, research has focused on newer targeted agents with the aim of decreasing the rates of side effects on healthy cells. Unfortunately, even targeted anticancer therapies show significant rates of toxicity on healthy tissue. mTOR inhibitors display some adverse events, such as hyperglycemia, hyperlipidemia, hypophosphatemia, hematologic toxicities, and mucocutaneous eruption, but the most important are still stomatitis and skin rash, which are often dose-limiting side effects.
Efficacy and safety of chimeric antigen receptor-T cells in the treatment of B cell lymphoma: a systematic review and meta-analysis. [2023]Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma. Since chimeric antigen receptor T-cell (CAR-T) technology has shown high safety and results in high remission rates, we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications.
Efficacy and safety of CD19 chimeric antigen receptor T cells in the treatment of 11 patients with relapsed/refractory B-cell lymphoma: a single-center study. [2022]No effective treatment exist for patients with relapsed and refractory B-cell lymphoma, until the advent of anti-CD19 chimeric antigen receptor (CAR) T-cells. Therefore, this study aimed to explore the factors affecting the efficacy of anti-CD19 CAR T-cell and the adverse reactions of the therapy.
Clinical experience of CAR T cell therapy in lymphomas. [2022]Non-Hodgkin lymphoma in relapse portends a poor prognosis due to resistance to cytotoxic chemotherapy and monoclonal antibodies. Chimeric Antigen receptor (CAR) T cell therapy has been tested in many lymphomas in the relapse refractory setting and has resulted in durable responses despite some peculiar side effects including cytokine release syndrome (CRS), neurological events (NE), prolonged cytopenias and hypogammaglobulinemia. This review summarizes the registration trials conducted in lymphomas. All products showed response rates that were far better than obtainable by salvage chemotherapy and most patients recovered from side effects including CRS and NEs. The impact of CAR T in the real world setting was discussed as well as how to approach the use of CAR T in special circumstances such as CNS involvement, management of post CAR relapses and outpatient therapy.
Low incidence of invasive fungal disease following CD19 chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma. [2022]CAR T-cell therapy has revolutionized the treatment of hematologic malignancies, although its use may be complicated by toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Invasive fungal disease (IFD) has been reported after CAR T-cell therapy, but the incidence in the absence of antifungal prophylaxis is unknown. Optimal prophylaxis strategies are widely debated. We performed a single-center retrospective study of 280 adults receiving CD19 CAR T-cell therapy for non-Hodgkin lymphoma (NHL) from December 2017 through September 2021. Patients did not receive routine antiyeast or antimold prophylaxis. IFD was identified between day of cell infusion and last follow-up. Cumulative incidence functions were calculated at 100 days and 18 months based on time to IFD, using dates of IFD-free death, initiation of salvage treatment, and hematopoietic cell transplantation as competing risks. Eight patients (2.9%) developed IFD, including 3 Pneumocystis jirovecii pneumonia, 3 invasive mold infections (IMIs), and 2 invasive yeast infections (IYIs). The 100-day cumulative incidence of IFD accounting for competing risks was 1.8% (95% confidence interval [CI], 0.8% to 4.4%). Among the 280 patients, early toxicities including CRS (85%) and ICANS (55%) and late toxicities after day 30 including grades 3 and 4 neutropenia (41%) and low CD4 T-cell count (20%) were common. IFD was rare among patients who received CD19 CAR T-cell therapy for NHL in the absence of routine antifungal prophylaxis, despite frequent toxicities. These results suggest that, in settings with low institutional rates of IFD, routine antifungal prophylaxis may not be indicated.
High-grade B-cell lymphoma (HGBL)-NOS is clinicopathologically and genetically more similar to DLBCL/HGBL-DH than DLBCL. [2023]High-grade B-cell lymphoma, not otherwise specified (HGBL-NOS) is rare and data focused on these neoplasms is lacking. We studied the clinicopathologic and genetic features of 136 HGBL-NOS patients and compared them to patients with DLBCL/HGBL-DH (n = 224, defined by 5th Edition WHO) and DLBCL (n = 217). HGBL-NOS patients had clinical features similar to DLBCL/HGBL-DH patients. MYC rearrangement (MYC-R) was present in 43% of HGBL-NOS. With induction regimen similar to DLBCL/HGBL-DH patients, HGBL-NOS patients had a median overall survival (OS) of 28.9 months, similar to DLBCL/HGBL-DH (p = 0.48) but inferior to DLBCL patients (p = 0.03). R-EPOCH induction was associated with improved OS compared with R-CHOP. MYC-R, history of lymphoma, and high IPI were independent adverse prognostic factors in HGBL-NOS patients. Whole transcriptome profiling performed on a subset of HGBL-NOS cases showed a profile more similar to DLBCL/HGBL-DH than to DLBCL; 53% of HGBL-NOS had a DH-like signature (DH-like-Sig) and were enriched for MYC-R. DH-like-Sig+ HGBL-NOS patients had a poorer OS than DH-like-Sig-negative patients (p = 0.04). In conclusion, HGBL-NOS has clinicopathologic features and a gene expression profile more similar to DLBCL/HGBL-DH than to DLBCL. Cases of HGBL-NOS frequently carry MYC-R and have a DH-like-Sig+. R-EPOCH induction in HGBL-NOS appears associated with improved OS compared with standard R-CHOP.
High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study. [2023]In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS.