CHO-H01 for Lymphoma
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Cho Pharma Inc.
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests CHO-H01, a new drug for non-Hodgkin's lymphoma, in patients whose cancer has returned or didn't respond to other treatments. The drug is given through an IV and targets cancer cells with a specific marker to destroy them.
Is the drug CHO-H01 a promising treatment for lymphoma?Yes, CHO-H01 is a promising treatment for lymphoma because it targets PD-1, an immune checkpoint receptor, which has shown remarkable activity in treating relapsed or refractory classic Hodgkin's lymphoma.158910
What safety data is available for CHO-H01 treatment in lymphoma?The safety data for CHO-H01, which may be related to PD-1 inhibitors like nivolumab and pembrolizumab, shows a favorable safety profile in treating relapsed/refractory classical Hodgkin's lymphoma (cHL). Studies indicate that immune-related adverse events are generally mild (grades 1-2), with some cases of more severe reactions (grades 3-4). These adverse events include gastrointestinal, hepatic, fever, hematological, dermatological, and allergic rhinitis issues. Toxicity resolved in all patients, and no deaths were attributed to the treatment. The incidence of immune-related adverse events was around 29%, with only a small percentage experiencing severe reactions. Overall, PD-1 inhibitors demonstrate good tolerance and efficacy in cHL treatment.411121314
What data supports the idea that CHO-H01 for Lymphoma is an effective treatment?The available research does not provide specific data on the effectiveness of CHO-H01 for Lymphoma. However, it mentions other treatments like brentuximab vedotin and nivolumab, which are effective for relapsed or resistant Hodgkin lymphoma. These treatments have shown promising results in increasing cure rates and reducing long-term side effects compared to traditional chemotherapy and radiation. This suggests that novel therapies targeting specific proteins in lymphoma cells can be effective.12367
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop all current medications, but you must be off anti-CD20 treatments for 30 days before starting CHO-H01. You cannot take systemic corticosteroids above 15 mg prednisone or equivalent within 14 days before starting the trial. Topical, inhaled, nasal, and ophthalmic steroids are allowed.
Eligibility Criteria
This trial is for adults with a specific BMI range who have relapsed or refractory CD20+ non-Hodgkin's lymphoma. They should be relatively active (ECOG 0-2), have measurable cancer, and not received certain treatments recently. Participants need good heart function, agree to birth control if applicable, and expect to live more than 12 weeks.Treatment Details
CHO-H01 is being tested in two parts: first to find the safest dose and then to see how well it works against the cancer. It's for those whose lymphoma has returned or didn't respond after treatment.
2Treatment groups
Experimental Treatment
Group I: CHO-H01+LenalidomideExperimental Treatment2 Interventions
Expansion phase with lenalidomide combination.
Phase2a:
Single cohort at Recommended Phase 2 Dose (RP2D) of CHO-H01.
Group II: CHO-H01Experimental Treatment1 Intervention
Dose escalation phase
Phase 1:
Five to six cohorts of escalating dose levels of CHO-H01 from 0.5mg/kg to 12 mg/kg.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Loading ...
Who is running the clinical trial?
Cho Pharma Inc.Lead Sponsor
References
First-line treatment of Hodgkin's lymphoma. [2007]Substantial clinical progress over the last decades has made Hodgkin's lymphoma (HL) into one of the most curable human cancers in adults. About 80% of patients in all stages and of all histological subtypes experience long-term disease-free survival. Modern treatment strategies aim to improve chemotherapy and radiotherapy, while minimizing therapy-related toxicities. Ongoing trials investigate a reduction of chemotherapy doses or cycles and the application of lower-radiation doses and smaller radiation field sizes. For patients with a specific high-risk profile, novel approaches with more intense drug combinations are currently being investigated in clinical trials. Here, we review recent approaches in the first-line treatment of early-favorable, early-unfavorable, and advanced-stage HL.
Novel agents in the therapy of Hodgkin lymphoma. [2018]Hodgkin lymphoma (HL) is a B-cell malignancy that typically has a favorable prognosis when treated with chemotherapy, often in combination with radiation therapy. The prognosis for patients whose disease relapses or is refractory, however, is far less favorable and novel therapies are needed for these patients. The unique cellular composition of HL provides a number of opportunities to target either the malignant Reed-Sternberg cell or the inflammatory tumor microenvironment. Antibody-drug conjugates targeting CD30, small molecule inhibitors of cell signaling, and antibodies that inhibit immune checkpoints, have all demonstrated activity in HL. Current and future trials are exploring the use of these agents in combination with each other and with standard chemotherapy.
[Clinical features and prognosis of CD20-positive classical Hodgkin lymphoma]. [2018]To explore the clinical characteristics and prognosis of CD20-positive classical Hodgkin lymphoma (CHL).
Checkpoint Inhibition in Hodgkin Lymphoma - a Review. [2018]Physiological immune checkpoint pathways are important to regulate self-tolerance, limit immune reactions, and moderate autoimmunity. Various cancers are commonly exploiting these mechanisms to evade the host immune system by restraining a durable, efficient anti-tumor immune response. Immune checkpoints include, but are not limited to, the programmed death 1 (PD1) and the cytotoxic T-lymphocyte-associated protein-4 (CTLA4) axis, which are both druggable by monoclonal antibodies referred to as checkpoint inhibitors (CIs). To date, the anti-PD1 antibodies nivolumab and pembrolizumab are approved for relapsed or refractory classical Hodgkin lymphoma (cHL) due to high response rates with a favorable yet distinct safety profile, and other agents are under investigation. This review summarizes the available preclinical and clinical data including the toxicity and efficacy of different CIs in cHL. It also provides future perspectives based on ongoing clinical trials, potentially synergistic combinatory approaches, and their fit in the therapeutic landscape in cHL.
PD-L1 Immunohistochemistry Highlights Bone Marrow Involvement by Classic Hodgkin Lymphoma in Staging Biopsies: Implications for Diagnosis and Tumor Microenvironment Alterations. [2020]Programmed cell death ligand 1 (PD-L1) is cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule. Previous studies have demonstrated consistent expression of PD-L1 by Reed-Sternberg (RS) cells, as well as nonmalignant tumor-infiltrating macrophages in classic Hodgkin lymphoma (CHL). Bone marrow involvement by CHL is uncommon, being present in 5% to 10% of cases, but indicates Ann Arbor stage IV disease. Given the mixed inflammatory infiltrate that characterizes CHL, detection of RS cells in small bone marrow biopsies may be difficult. We sought to investigate the diagnostic utility of PD-L1 expression in staging bone marrow biopsies from patients with newly diagnosed CHL. Forty-four staging bone marrow biopsies from patients with newly diagnosed CHL were examined for PD-L1 expression by immunohistochemistry. Eight bone marrow biopsies were positive for involvement by CHL (8/44, 18%) and all were positive for PD-L1 (8/8, 100%), including a case that was originally nondiagnostic. Membranous PD-L1 expression was restricted to RS cells and the adjacent nontumor inflammatory cells admixed within areas of fibrosis. Uninvolved bone marrow biopsies and normal-appearing marrow in cases positive for CHL were negative for PD-L1. In comparison, bone marrow biopsies with myelofibrosis caused by myeloproliferative or myelodysplastic disorders were negative for significant PD-L1 staining. PD-L1 expression in RS cells and surrounding inflammatory cells is a sensitive marker for bone marrow involvement by CHL. In cases where RS cells are infrequent, PD-L1 staining in regions of fibrosis may serve as a useful diagnostic clue to involvement by CHL.
Advances in CD30- and PD-1-targeted therapies for classical Hodgkin lymphoma. [2020]CD30 and programmed cell death protein 1 (PD-1) are two ideal therapeutic targets in classical Hodgkin lymphoma (cHL). The CD30 antibody-drug conjugate (ADC) brentuximab vedotin and the PD-1 antibodies nivolumab and pembrolizumab are highly efficacious in treating relapsed and/or refractory cHL. Ongoing studies are evaluating their efficacy in earlier lines of therapy and have demonstrated encouraging results. These agents are expected to further change the landscape of cHL management. Increased cure rates and reduced long-term toxicity from traditional chemotherapy and radiotherapy are likely with the emergence of these novel targeted therapies.
Efficacy of nivolumab as checkpoint inhibitor drug on survival rate of patients with relapsed/refractory classical Hodgkin lymphoma: a meta-analysis of prospective clinical study. [2022]The primary standard treatment for classic Hodgkin's lymphoma (cHL) is chemotherapy and radiation therapy. However, some patients get relapsed, or their diseases become resistant. PD1 blocking antibodies have been used to increase the response of treatment in solid tumors, and led to potentially stable responses that are acceptable. Our purpose in this study is to investigate the effect of nivolumab as a PD1 blocking antibody on the survival rate of patients with Hodgkin's cancer.
Safety and Efficacy in Relapsed or Refractory Classic Hodgkin's Lymphoma Treated with PD-1 Inhibitors: A Meta-Analysis of 9 Prospective Clinical Trials. [2022]Classic Hodgkin's lymphoma (cHL) is characterized by the unique biology in which rare Hodgkin-Reed-Sternberg cells propagate an immunosuppressive microenvironment. Checkpoint inhibitors that target the interaction of PD-1 immune checkpoint receptors have demonstrated remarkable activities in various cancers, such as cHL. This study aims to evaluate the safety and efficacy of PD-1 inhibitors in treating relapsed or refractory cHL (rrHL).
Effectiveness of chemotherapy after anti-PD-1 blockade failure for relapsed and refractory Hodgkin lymphoma. [2021]Programmed death-1 (PD1) blockade is an efficient and safe therapeutic option in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, a substantial proportion of patients' progresses or loses the response to anti-PD1 treatment. We retrospectively investigated the effectiveness of salvage chemotherapies (CHT) for unsatisfactory response to anti-PD1, in 25 R/R cHL patients. Twenty-three patients (92%) were refractory to the last treatment before anti-PD1. After a median of 14 cycles (range 3-52), 68% (17/25) of patients had unsatisfactory responses to anti-PD1 therapy, whereas 6 had a partial response (PR) and 2 patients achieved complete response (CR), with an overall response rate (ORR) of 32%. After a median time of 1.5 months, 15 patients received a single agent treatment and 10 had a multi-agents regimen, due to the failure of PD1 blockade. The ORR was 60% (8 CR and 7 PR). Seven patients (3 in PR and 4 in CR) underwent a consolidation strategy with stem cell transplantation. Median progression-free survival (PFS) with salvage treatment was reached at 19.1 months, while median PFS after anti-PD1 has been reached at 8.2 months. After a median follow-up of 32.4 months, 6 patients died while 13 are still in CR. The median overall estimated from the start of CHT was not reached. The efficacy of treatment following anti-PD1 is not yet established, especially in lymphoma patients. To note, in our series, a subset of heavily pre-treated and chemo-refractory patients increased response rates to and survival with CHT given after exposure to immune-checkpoint inhibitors.
Lymphocyte-depleted classic Hodgkin lymphoma with primary extranodal disease: Two cases that highlight the combination of immunodeficiency and immune escape in the pathogenesis. [2021]Neoplastic programmed cell death ligand 1 (PD-L1) expression, activated by PD-L1 gene alterations, is strongly associated with classic Hodgkin lymphoma (CHL). This association enabled a diagnostic consensus for lymphocyte-depleted CHL (LD-CHL), a previously enigmatic disease. We describe two patients with LD-CHL and primary extranodal disease. One patient was a 92-year-old female (Case #1) with a large mass that involved the uterus combined with swollen lymph nodes in the pelvic cavity. The second patient was a 76-year-old female (Case #2) with human T-cell leukemia virus type 1 (HTLV-1) who initially exhibited massive bone marrow involvement without peripheral lymphadenopathies. Biopsies of these tumors from the cervix uteri and bone marrow, respectively, revealed lesions rich in Hodgkin and Reed-Sternberg (H-RS) cells and diminished populations of other cell populations. Immunohistochemistry demonstrated that these H-RS cells expressed CD30, BOB1, and fascin, but not CD15, CD20, PAX5, or OCT2. They also expressed PD-L1, which led to our preferred diagnosis of LD-CHL in both patients. Epstein-Barr virus was associated with LD-CHL in Case #1, but not in Case #2. Both patients were deemed too frail for treatment. They died of disease at 1 (Case #1) and 15 months (Case #2) after the diagnosis. These findings highlight the abnormal biological behavior of this immune-escape-related lymphoid neoplasm in patients with immunodeficiency due to immune senescence and HTLV1 infection.
Anti-programmed cell death-1 monoclonal antibody therapy before or after allogeneic hematopoietic cell transplantation for classic Hodgkin lymphoma: a literature review. [2022]Approximately 10-30% of patients with classic Hodgkin lymphoma (cHL) have relapsed or refractory (r/r) disease after standard first-line therapy. Clinical trials have shown an acceptable safety profile and high response rate for anti-programmed cell death-1 monoclonal antibodies (anti-PD-1 mAbs) in patients with r/r cHL. Although anti-PD-1 mAbs have significantly increased treatment options for r/r cHL, most patients eventually relapse. In the current era, allogeneic hematopoietic cell transplantation (allo-HCT) is still a clinical option for r/r cHL. Anti-PD-1 mAbs have been explored as bridging therapy to allo-HCT and salvage therapy for relapse after allo-HCT. Although early reports showed increased risks of severe graft-versus-host disease (GVHD) in patients who received anti-PD-1 mAb before or allo-HCT, survival outcomes were favorable, suggesting the feasibility of PD-1 blockade around the time of allo-HCT. Based on clinical and biological data, posttransplant cyclophosphamide-based GVHD prophylaxis is a promising strategy to reduce GVHD and improve survival after allo-HCT following PD-1 blockade. Close monitoring and early intervention are needed for treatment-emergent GVHD following PD-1 blockade after allo-HCT. Further studies with a larger cohort and extended follow-up will provide insights into better patient selection, optimal dosing, and strategies to manage complications of PD-1 blockade in the context of allo-HCT.
A real-world analysis of PD1 blockade from the Rete Ematologica Pugliese (REP) in patients with relapse/refractory Hodgkin's lymphoma. [2023]Checkpoint inhibitors have significantly changed the prognosis of patients with relapsing refractory classical Hodgkin's lymphoma (cHL), demonstrating excellent results in heavily pretreated patients. However, there is still limited data on the real-world experience with PD-1 inhibitors in cHL. Within the context of the Apulian hematological network (Rete Ematologica Pugliese, REP), we performed a retrospective, multicenter analysis of 66 patients with relapsing refractory cHL who had received PD-1 inhibitors in the non-trial setting. Forty-three patients (65%) were treated with nivolumab and 23 (35%) with pembrolizumab. Thirty-one (47%) and 8 (12%) patients underwent autologous or allogeneic stem cell transplantation prior to checkpoint inhibitor therapy, respectively. The median number of lines of treatment attempted prior to PD-1 inhibitor therapy was 4 (range, 3 to 7). All patients had received brentuximab vedotin prior to checkpoint inhibitor therapy. The overall response rate to PD-1 inhibitors therapy was 70% (47% complete remission (CR) and 23% partial remission (PR)). Twenty-four immune-related adverse events (19 (80%) grades 1-2; 5 (20%) grades 3-4) were documented (4 gastrointestinal, 4 hepatic, 6 fever, 4 hematological, 3 dermatological, 3 allergic rhinitis). Toxicity resolved in all patients, and there were no deaths attributed to checkpoint inhibitor therapy. After a median follow-up of 26 months (range 3-72 months), 54 patients (82%) are alive, and 12 (18%) died. The cause of death was attributed to disease progression in 9 patients and sepsis in 3 patients. After PD-1 inhibitor therapy, 22 patients (33%) relapsed or progressed. The overall survival and progression-free survival at 5 years were 65% and 54%, respectively. This study confirms the efficacy and tolerability of PD-1 inhibitor therapy in relapsed refractory cHL in a real-world setting, demonstrating similar clinical outcomes and toxicity profiles compared to clinical studies.
Long-term survival benefit of anti-PD-1 therapy in patients with relapsed or refractory classical Hodgkin lymphoma. [2023]Anti-programmed cell death-1 (anti-PD-1) therapies have shown a favorable efficacy and good tolerance for relapsed or refractory (r/r) classical Hodgkin lymphoma (cHL). However, there are limited data on long-term outcomes among patients with r/r cHL who achieve an objective response to anti-PD-1 therapies. A total of 260 responders from four, phase 2 clinical trials were included in this study. The median age was 32 years with a male/female ratio of 1.3:1. After a median follow-up period of 31.1 months, 116 (44.6%) responders experienced disease progression and 18 (6.9%) died. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 55.1% and 89.7% overall. Patients with partial remission (PR) had inferior outcomes compared with those who achieved complete remission (3-year PFS, 29.5% vs. 72.3%, P
[Efficacy and safety of programmed death-1 inhibitor in the treatment of relapsed/refractory classical Hodgkin's lymphoma]. [2023]Objective: This retrospective, single-center study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitors, either as monotherapy or in combination with chemotherapy, in the management of relapse/refractory classical Hodgkin's lymphoma (R/R cHL) . Methods: A total of 35 patients with R/R cHL who received treatment at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from September 2016 to December 2020 were enrolled in this study. Among them, 17 patients received PD-1 inhibitor monotherapy (PD-1 inhibitor group), while 18 patients received a combination of PD-1 inhibitor and chemotherapy (PD-1 inhibitor + chemotherapy group). Clinical data and follow-up information were retrospectively analyzed, and survival analysis was conducted using the Kaplan-Meier method and Cox proportional hazards model. Results: The median age of the 35 patients with R/R cHL was 29 years (range: 11-61 years), with 54.3% being male. According to the Ann Arbor staging system, 62.9% of patients presented with advanced (stage Ⅲ/Ⅳ) disease, and 48.6% had extranodal involvement. Before PD-1 inhibitor therapy, the median number of prior lines of therapy was 2 (range: 1-3). Objective responses were observed in 28 patients, including 22 complete response (CR) cases, resulting in an overall response rate (ORR) of 80.0% and a CR rate of 62.9%. Specifically, the ORR and CR rates were 64.7% and 58.8%, respectively, in the PD-1 inhibitor group and 94.4% and 66.7%, respectively, in the PD-1 inhibitor + chemotherapy group. Among the 18 patients who underwent sequential autologous hematopoietic stem cell transplantation (auto-HSCT) [13 CR and five partial response (PR) cases], eight patients received PD-1 inhibitor therapy after auto-HSCT as consolidation therapy. All patients maintained a CR status after transplantation, and they exhibited significantly improved progression-free survival (PFS) rates compared with those who did not undergo sequential auto-HSCT (4-year PFS rates: 100% vs 53.5% ; P=0.041). The incidence of immune-related adverse events was 29%, with only one patient experiencing grade≥3 adverse reactions, which indicated a favorable safety profile for the treatment approach. Conclusions: PD-1 inhibitor monotherapy demonstrates notable efficacy and sustained response in patients with R/R cHL. PD-1 inhibitors combined with chemotherapy significantly improve response rates. Additionally, for salvage therapy-sensitive patients, consolidation treatment with PD-1 inhibitors after auto-HSCT exhibits the potential for prolonging PFS.