Immunotherapy for Hodgkin's Lymphoma
Recruiting in Palo Alto (17 mi)
+33 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Immunosuppressants, Investigational agents
Disqualifiers: Classical Hodgkin lymphoma, CNS involvement, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing a new treatment called mosunetuzumab against the usual treatment, rituximab, for patients with a type of cancer called NLPHL. Both treatments help the immune system find and kill cancer cells by targeting a specific protein on these cells. The goal is to see if mosunetuzumab can improve survival better than rituximab.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic immunosuppressive medications within 2 weeks before starting the study treatment.
What data supports the effectiveness of the drug Rituximab for treating Hodgkin's Lymphoma?
Rituximab has shown effectiveness in treating certain types of non-Hodgkin's lymphoma and has been used in combination with other treatments for relapsed and refractory Hodgkin lymphoma, suggesting potential benefits in similar conditions.
12345What safety information is available for immunotherapy treatments like Rituximab and similar drugs?
Rituximab, a type of immunotherapy, has been used for over 10 years and is generally safe, but it can increase the risk of infections, especially in people with weakened immune systems. Common side effects of monoclonal antibodies like Rituximab include flu-like symptoms during the first infusion, and there is a risk of serious infections like hepatitis B reactivation and a rare brain infection called PML.
678910How is the drug Mosunetuzumab, Rituximab unique for treating Hodgkin's Lymphoma?
Mosunetuzumab is a novel drug that works by engaging the body's immune system to target and destroy cancer cells, while Rituximab is a well-established antibody that targets a specific protein on B cells. This combination may offer a new approach for treating Hodgkin's Lymphoma by potentially enhancing the immune response against the cancer.
15111213Eligibility Criteria
This trial is for adults with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), either untreated or previously treated but not within the last 6 months if rituximab was used. Participants need to have symptoms like fever, weight loss, night sweats, or measurable disease and can't just be observed. They must also have good organ function and performance status.Inclusion Criteria
Patients must have measurable disease according to the Lugano/LYRIC classification
Agreement to use adequate contraception by women of childbearing potential and men
Ability to understand and sign a written informed consent document
+16 more
Exclusion Criteria
Uncontrolled intercurrent illness or significant conditions making participation hazardous
I have or might have a long-term EBV or CMV infection.
I have not had infections needing IV treatment in the last 4 weeks.
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either mosunetuzumab or rituximab. Mosunetuzumab is administered subcutaneously on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles, repeating every 21 days for up to 8 cycles. Rituximab is administered intravenously on day 1 and with hyaluronidase human subcutaneously on days 8, 15, and 22 of each cycle, repeating every 28 days for up to 2 cycles.
8-16 weeks
Multiple visits for drug administration and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 6 months for 2 years.
2 years
Follow-up visits every 6 months
Crossover
Participants experiencing disease progression may crossover to the alternate treatment arm at week 12.
Until disease progression or unacceptable toxicity
Participant Groups
The study compares mosunetuzumab with the usual treatment of rituximab in improving survival for NLPHL patients. Both drugs are monoclonal antibodies targeting CD20 on B cells and cancer cells, potentially helping the immune system destroy these cells.
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm I (Mosunetuzumab)Experimental Treatment7 Interventions
Patients receive mosunetuzumab SC on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience PD will be permitted to crossover to arm II at week 12. Patients also receive FDG and undergo PET/CT at baseline and end of treatment. Patients who are positive at pre-treatment bone marrow biopsy also receive FDG and undergo PET/CT on study. Patients also undergo bone marrow biopsy and tissue biopsy at baseline, and blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy and tissue biopsy at end of treatment.
Group II: Arm II (Rituximab, Rituximab and hyaluronidase human)Active Control8 Interventions
Patients receive rituximab IV on day 1 and rituximab and hyaluronidase human SC on days 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 2 cycles 8 weeks apart in the absence of disease progression or unacceptable toxicity. Patients may receive rituximab IV on days 8, 15, and 22 of each cycle if rituximab and hyaluronidase human is not available. Patients who experience PD will be permitted to crossover to arm I at week 12. Patients also receive FDG and undergo PET/CT at baseline and end of treatment. Patients who are positive at pre-treatment bone marrow biopsy also receive FDG and undergo PET/CT on study. Patients also undergo bone marrow biopsy and tissue biopsy at baseline, and blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy and tissue biopsy at end of treatment.
Mosunetuzumab is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Lunsumio for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
🇺🇸 Approved in United States as Lunsumio for:
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Huntsman Cancer Institute/University of UtahSalt Lake City, UT
University of Pittsburgh Cancer Institute (UPCI)Pittsburgh, PA
University of Texas MD Anderson Cancer Center LAOHouston, TX
University of Cincinnati Cancer Center-West ChesterWest Chester, OH
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Transformation of Hodgkin's disease to high-grade B-cell lymphoma: remission after Rituximab monotherapy. [2020]We demonstrate the usefulness of immunotherapy with the CD20 antibody Rituximab in a case of transformation of Hodgkin's disease (HD) to high-grade non-Hodgkin's lymphoma (NHL).
[Rituximab combined with second line regimens for treatment of seven relapsed and refractory Hodgkin lymphoma patients]. [2020]To investigate the efficacy and safety of Rituximab combined with second line regimen for treatment of relapsed and refractory Hodgkin lymphoma.
Rituximab: clinical development and future directions. [2019]The availability of effective monoclonal antibodies (mAbs) has revolutionised the management of patients with B-cell malignancies. The most widely studied of these agents is rituximab (Rituxan, IDEC Pharmaceuticals, San Diego, CA), a chimeric anti-CD20 antibody. Using the standard 4-weekly administration schedule, rituximab induces responses in almost half of patients with relapsed follicular/low-grade (F/LG) non-Hodgkin's lymphoma (NHL) with complete remissions in 6%. Lower response rates (RRs) have been noted in chronic lymphocytic leukaemia (CLL) using the standard dose and schedule. The drug has been well tolerated in most patients with common adverse events including mild to moderate fevers and chills and rare occurrences of a serious syndrome related to cytokine release and rapid tumour clearance. This antibody is also active against aggressive NHL, mantle cell NHL, post-transplant lymphoproliferative disorder (PTLD), lymphoplasmacytic NHL and hairy cell leukaemia and is also being evaluated in autoimmune disorders. Combinations of rituximab with chemotherapy regimens such as CHOP (cyclophosphamide, adriamycin, vincristine, predinisone) may alter the therapeutic paradigm for these diseases. The future promise of this antibody is a foundation on which to develop new strategies to increase the cure of patients with lymphoid malignancies.
Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. [2015]Rituximab (Rituxan) was the first monoclonal antibody approved for cancer therapy and the first single-agent approved for therapy of lymphoma. When combined with CHOP, rituximab is the only drug that has been shown to improve survival of a subpopulation of patients with diffuse large cell lymphoma during the last three decades. It was approved by the FDA for the treatment of patients with relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma in 1997. Rituximab is also being studied in many other B-cell malignancies alone and in combination with other agents. Furthermore, it is currently being evaluated in several nonmalignant diseases, such as autoimmune disorders. This review will focus on the role of rituximab in patients with non-Hodgkin's lymphoma.
Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. [2022]Rituximab is commonly used as a single agent or in combination therapy for non-Hodgkin's lymphoma (NHL). Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-naïve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL.
Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence? [2021]Introduction of the monoclonal antibody rituximab to chemotherapy regimens has substantially improved disease-free and overall survival in patients with non-Hodgkin lymphomas (NHL). The short-term safety of this drug has been widely reported, but there are few data on long-term safety, which suggests that these patients require prolonged follow-up.
[Toxicity of targeted therapies and immunotherapy with checkpointinhibitors in Hodgkin lymphoma]. [2023]TOXICITY OF TARGETED THERAPIES AND IMMUNOTHERAPY WITH CHECKPOINT INHIBITORS IN HODGKIN LYMPHOMA. In patients at increased risk of recurrence or progression after autotransplantation, or in cases of relapse after autotransplantation or after at least two lines of treatment when intensive multidrug therapy is no longer a treatment option, targeted anti-CD30 therapy with brentuximab vedotin may be proposed. Brentuximab vedotin is a monoclonal antibody directed against CD30 and coupled with an anti-microtubule cytotoxic agent, monomethyl auristatin E (MMAE). The main adverse side effect of brentuximab vedotin is peripheral neuropathy. In patients who have relapsed after intensive chemotherapy, including autograft for patients eligible for this treatment, and after failure of brentuximab vedotin, anti-PD1 immunotherapy (nivolumab or pembrolizumab) may be offered. Anti-PD1 (Programmed cell death protein 1) side effects are immune-related, varied and unpredictable (endocrinopathies, rash, colitis, interstitial lung disease). The tolerability profiles of brentuximab vedotin and anti-PD1 and the management of the main undesirable side effects of these treatments are detailed for clinical practice.
Unique aspects of supportive care using monoclonal antibodies in cancer treatment. [2020]The "magic bullet" era of targeted cancer therapy began with the United States Food and Drug Administration approval of rituximab for the treatment of B-cell lymphoma in the late fall of 1997. Since then, several additional anticancer antibody products have received regulatory approval, including the monoclonal antibodies (MoAbs) trastuzumab for breast cancer and alemtuzumab for chronic lymphocytic leukemia, and the MoAb immunoconjugates gemtuzumab ozogamicin for acute myelogenous leukemia and yttrium 90 ibritumomab tiuxetan for B-cell lymphoma. These products are associated with adverse events that are quite different than those seen with chemotherapy. Adverse events associated with MoAb products typically have 1 of 3 etiologies: direct and indirect effects of antibody-antigen interaction, effects of toxins or radioisotopes that have been conjugated to antibodies, and allergic and hypersensitivity reactions to foreign protein. The infusion-related symptom complex is the most common and predictable side effect associated with all MoAbs that react with circulating blood cells. This pattern of various systemic effects includes flu-like symptoms such as headache, shortness of breath, fever, skin rash, hypotension, nausea, and asthenia, but usually occurs only in association with the first of any series of weekly infusions. The severity of these reactions is influenced by the rate of infusion, and the syndrome is the consequence of cytokines released from immune cells. Severe hypotension, bronchospasm, hypoxia, and even death have occurred. A true tumor lysis syndrome may occur if there are large numbers of proliferating antigen-positive cells in the blood. Symptoms related to the infusion reaction are ameliorated by slowing or stopping the infusion and administering antiinflammatory agents and antihistamines.
Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab. [2015]The aim of this study was to analyse the suspected adverse reactions associated with rituximab or trastuzumab reported to the Spanish Pharmacovigilance System.
Rituximab-associated infections. [2020]After more than 10 years of use, rituximab has proven to be remarkably safe. However, accumulated evidence now suggests that under some circumstances it may significantly increase the risk of infections. This risk is difficult to quantify because of confounding factors (namely, concomitant use of immunosuppressive or chemotherapeutic agents and underlying conditions), as well as under-reporting. Increased number of infections has been documented in patients treated with maintenance rituximab for low-grade lymphoma and in patients with concomitant severe immunodeficiency, whether caused by human immunodeficiency virus (HIV) infection or immunosuppressive agents like fludarabine. From the practical standpoint, the most important infection is hepatitis B reactivation, which may be delayed and result in fulminant liver failure and death. Special care should be placed on screening for hepatitis B virus (HBV) and preemptive antiviral treatment. Some investigators have reported an increase in Pneumocystis pneumonia. Finally, there is increasing evidence of a possible association with progressive multifocal leukoencephalopathy (PML), a lethal encephalitis caused by the polyomavirus JC. This review enumerates the described infectious complications, summarizes the possible underlying mechanisms of the increased risk, and makes recommendations regarding prevention, diagnosis and management.
Use of rituximab, the new FDA-approved antibody. [2019]Rituximab (Rituxan; IDEC Pharmaceuticals, San Diego, CA) is the first monoclonal antibody approved by the US Food and Drug Administration for the treatment of cancer. It is a genetically engineered chimeric (murine-human) monoclonal antibody (mAb) directed against the CD20 antigen found on the surface of normal and malignant B cells. Multicenter studies have demonstrated its efficacy against relapsed low-grade and follicular non-Hodgkin's lymphoma (NHL). The mAb demonstrated tolerable side effects, primarily limited to fevers and chills associated with the first infusion. The currently recommended dosage is 375 mg/m2/infusion, given weekly for 4 weeks. Because of its human component, rituximab has low immunogenicity and should not significantly hinder future retreatment. Future studies will evaluate the antitumor activity of rituximab combined with various other chemotherapeutic or biologic agents in the treatment of B-cell lymphoma and other CD20-positive lymphoid neoplasms.
Rituximab and its role as maintenance therapy in non-Hodgkin lymphoma. [2015]Since rituximab, a chimeric monoclonal anti-CD20 antibody, was introduced into clinical practice in 1997, data regarding its benefit in terms of response rate, quality of response, progression-free survival and overall survival in B-cell lymphoid malignancies continues to expand. Rituximab has proven to be a relatively well-tolerated drug, with its major side effects being infusion related. Rituximab was approved initially by the US FDA and the European Medicines Agency for relapsed or refractory low-grade or follicular CD20+ B-cell non-Hodgkin lymphomas. Subsequently, its use has been extended to include first-line therapy in low-grade lymphoma as well as the treatment of more aggressive histological subtypes such as diffuse large B-cell lymphoma. In this article, we review the landmark trials that have impacted clinical practice in follicular and diffuse large B-cell lymphomas and the emerging data for use of rituximab as maintenance therapy in non-Hodgkin lymphoma.
[Role of anti-CD20 monoclonal antibody in association with immunomodulatory agents]. [2017]Chimeric monoclonal anti-CD20 antibody (Rituximab) has been associated with immunomodulatory agents such as interferon alpha, interleukin-2, interleukin-12, G-CSF, GM-CSF and anti-CD22 humanized monoclonal antibody (Epratuzumab). Synergy with interferon is clearly demonstrated increasing complete response rate and response duration. Other associations are promising but must be tested in randomized prospective trials versus rituximab alone, probably in indolent lymphomas where chemotherapy could be avoided.