CC-99282 + Rituximab for Non-Hodgkin's Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Nathan Denlinger
Must not be taking: CYP3A inhibitors, CYP3A inducers
Disqualifiers: Pregnancy, Breastfeeding, Heart failure, others
No Placebo Group
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase I trial tests the safety, side effects and best dose of CC-99282 with rituximab for the treatment of patients who have received chimeric antigen receptor (CAR) T cell therapy for non-Hodgkins lymphoma and in whom have had a sub-optimal response early on to CAR T-cell therapy. Immunotherapy with CC-99282 may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving CC-99282 with rituximab may be a safe and effective treatment option for patients who have received CAR-T cell therapy for relapsed or refractory non-Hodgkin's lymphoma.
Will I have to stop taking my current medications?
You may need to stop taking certain medications, especially strong CYP3A inhibitors and inducers, before joining the trial. If you are on moderate CYP3A inhibitors or inducers, a washout period (time without taking these medications) of at least 14 days or 5 half-lives is required before starting the study treatment.
What data supports the effectiveness of the drug Rituximab for treating non-Hodgkin's lymphoma?
Rituximab has been shown to improve survival in patients with non-Hodgkin's lymphoma when added to standard chemotherapy, and it induces responses in almost half of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma. It is effective as a single agent or in combination with other treatments, providing long-term remissions and improved survival rates.
12345Is the combination of CC-99282 and Rituximab safe for humans?
Rituximab has been used in many patients and is generally well-tolerated, with common side effects like fevers and chills during the first infusion. Serious reactions are rare but can include heart and lung issues, especially in patients with high numbers of cancer cells or existing heart problems.
13678What makes the drug CC-99282 + Rituximab unique for treating non-Hodgkin's lymphoma?
The combination of CC-99282 with Rituximab is unique because Rituximab is a monoclonal antibody that targets the CD20 antigen on B-cells, which is effective in treating various B-cell non-Hodgkin's lymphomas, and CC-99282 may enhance this effect, potentially offering a novel approach to treatment.
1291011Eligibility Criteria
This trial is for patients with various types of Non-Hodgkin's Lymphoma who have had a less than ideal response to CAR T-cell therapy. It's important that participants haven't responded well to this prior treatment and are now looking for additional options.Inclusion Criteria
Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information
I am 18 years old or older.
Aspartate aminotransferase (AST) ≤ 3.0 × ULN (obtained within 14 days prior to initiating study treatment)
+20 more
Exclusion Criteria
I have not received CD19.CAR-T therapy for conditions outside those specified.
I am not using strong medication that affects liver enzymes.
I do not have severe heart problems, uncontrolled seizures, or very high blood pressure.
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Patients receive rituximab IV on day 1 of each cycle and CC-99282 PO QD on days 1-14 of each cycle. Treatment repeats every 28 days for up to 6 cycles of rituximab and up to 24 cycles of CC-99282.
24 months
Monthly visits for up to 24 cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
24 months
Visits at days 240, 365, 455, 547, 637, and 730
Participant Groups
The trial is testing the combination of a new immunotherapy drug, CC-99282, with an established cancer drug called Rituximab. The study aims to find the safest dose and observe how these drugs affect the immune system in attacking lymphoma cells post CAR-T therapy.
1Treatment groups
Experimental Treatment
Group I: Treatment (rituximab, CC-99282)Experimental Treatment6 Interventions
Patients receive rituximab IV on day 1 of each cycle and CC-99282 PO QD on days 1-14 of each cycle. Treatment repeats every 28 days for up to 6 cycles of rituximab and up to 24 cycles of CC-99282 in the absence of disease progression or unacceptable toxicity. Patients also undergo PET/CT and collection of blood samples throughout the trial. Patients may undergo biopsy at screening.
Rituximab is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Rituxan for:
- Non-Hodgkin's lymphoma
- Chronic lymphocytic leukemia
- Rheumatoid arthritis
- Granulomatosis with polyangiitis
- Microscopic polyangiitis
🇪🇺 Approved in European Union as MabThera for:
- Non-Hodgkin's lymphoma
- Chronic lymphocytic leukemia
- Rheumatoid arthritis
- Granulomatosis with polyangiitis
- Microscopic polyangiitis
🇨🇦 Approved in Canada as Rituxan for:
- Non-Hodgkin's lymphoma
- Chronic lymphocytic leukemia
- Rheumatoid arthritis
- Granulomatosis with polyangiitis
- Microscopic polyangiitis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Ohio State University Comprehensive Cancer CenterColumbus, OH
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Who Is Running the Clinical Trial?
Nathan DenlingerLead Sponsor
Bristol-Myers SquibbIndustry Sponsor
References
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.
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.
Long-term molecular remissions in patients with indolent lymphoma treated with rituximab as a single agent or in combination with interferon alpha-2a: a randomized phase II study from the Nordic Lymphoma Group. [2021]The purpose of this phase II randomized trial was to evaluate the effect and safety of interferon-alpha2a (IFN) in combination with extended dosing rituximab in patients with symptomatic, advanced indolent lymphoma responding to a standard single course of rituximab. Totally 123 patients were treated with rituximab 375 mg/m2 once weekly for 4 weeks leading to 14 complete response (CR; 11%), 56 partial response (PR; 46%), and 13 minor responses (MR; 11%). Patients achieving either PR or MR were randomized to four more infusions of rituximab alone (n = 36) or in combination with five weeks of IFN (n = 33), with an overall response rate (CR + PR) of 78% and 94%, respectively. Significantly more patients in the combination arm improved their response from PR/MR to CR (P or = 24 months (72% versus 50%), respectively. Overall, 26 out of the 52 patients who achieved CR underwent minimal residual disease (MRD) evaluation. Totally 17 of these (65%) achieved MRD negativity, 14 of whom remain in CR after 4.8 years' follow-up. The addition of IFN to rituximab was generally safe, but reversible thrombocytopenia and neutropenia were noted in one and six patients, respectively, requiring a reduction in the IFN dose. Extended rituximab is effective and well tolerated and combination with IFN seems to improve both the quality and duration of the responses, providing the opportunity to achieve long-term molecular CRs and prolonged failure-free survival without chemotherapy.
Review of the safety and feasibility of rapid infusion of rituximab. [2022]Added to standard chemotherapy, rituximab improved survival in patients with non-Hodgkin's lymphoma; added to fludarabine-based regimens, it improved response and survival in patients with chronic B-cell lymphocytic leukemia.
Rituximab in lymphoma: a systematic review and consensus practice guideline from Cancer Care Ontario. [2018]Rituximab is the first antibody-based therapy approved in cancer. The role of this treatment for non-Hodgkin's lymphoma has evolved significantly since its introduction. We aimed to systematically review the literature on rituximab in non-Hodgkin's lymphoma and provide consensus guidelines as to the rational use of this agent. Validated methodology from the Cancer Care Ontario Program in Evidence-Based Care was applied. A comprehensive literature search was completed by reviewers from the Hematology Disease Site Group of Cancer Care Ontario. Data were abstracted from randomized controlled trials of rituximab-containing regimens for patients with non-Hodgkin's lymphoma. Twenty-three randomized controlled trials (RCTs) of rituximab-based therapy were analyzed. Consistent and clinically important benefits in progression-free and overall survival and were seen in the following settings: (1) addition of rituximab to combination chemotherapy for initial treatment of diffuse large B-cell lymphoma and other aggressive B-cell lymphomas; (2) addition of rituximab to combination chemotherapy for initial and subsequent treatment of follicular lymphoma and other indolent B-cell lymphomas; and (3) use of rituximab alone as extended maintenance therapy in patients with indolent B-cell lymphomas who have responded to initial treatment. The consensus opinion of the Hematology Disease Site Group is that rituximab is recommended for these indications.
Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. [2022]To determine the safety and efficacy of the combination of the chimeric anti-CD20 antibody, Rituxan (Rituximab, IDEC-C2B8; IDEC Pharmaceuticals Corporation, San Diego, CA), and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy.
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.
Optimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update. [2022]Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA), the first monoclonal antibody approved in the United States for the treatment of cancer, is indicated for the treatment of patients with relapsed or refractory CD20+ low-grade non-Hodgkin's lymphoma. From November 1997 through May 1999, approximately 36,000 patients have been treated with rituximab. Serious cardiopulmonary infusion reactions culminating in death have been reported to occur in approximately 0.04% to 0.07% of patients. Post-approval tumor lysis syndrome has been reported within 12 to 24 hours after the first antibody infusion and is estimated to occur in 0.04% to 0.05% of patients. The risk of tumor lysis appears to be higher in patients with high numbers of circulating malignant cells. Serious infusion-related adverse drug reactions, most often consisting of cardiopulmonary reactions associated with the rapid lysis of large numbers of circulating malignant cells, have been fatal in approximately 0.5 per 1,000 treated patients. Major risk factors include high numbers of circulating malignant lymphoma cells, pulmonary infiltrates or lymphoma involvement, and prior cardiovascular disease. This report updates the safety experience of rituximab therapy with data from clinical trials and postmarketing safety experience, and examines how this information can be used to optimize therapy.
Rituximab in combination with vinorelbine/gemcitabine chemotherapy in patients with primary refractory or early relapsed T cell rich B cell lymphoma. A pilot study. [2022]Rituximab is a chimeric monoclonal antibody that binds specifically to the CD20 antigen expressed in most B cell lymphomas. As single agent or in combination with chemotherapy rituximab has shown significant activity in patients with relapsing or refractory aggressive lymphomas. Because T cell rich B cell lymphomas (TCRBCL) also express the CD20 antigen, we decided to evaluate the efficacy and tolerability of the anti-CD20 monoclonal antibody rituximab combined with chemotherapy in four patients with either primary refractory or early relapsed TCRBCL. The chemotherapy regiment consisted of vinorelbin and gemcitabine, a combination with known efficacy in patients with refractory aggressive lymphomas. The patients received 6 cycles of rituximab at the dose of 375 mg/m(2), combined with vinorelbine 25 mg/m(2) and gemcitabine 800 mg/m(2) at 3-week intervals. Three complete responses and one partial response were observed among our four patients with refractory or early relapsed TCRBCL without significant adverse effects, indicating considerable efficacy of this combination. Therefore, rituximab should be tested in combination with chemotherapy in the front line treatment of patients with TCRBCL.
[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. [2015]Excellent results were reported for dose-dense and dose-intense weekly combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, etoposide and additional ara-C) (CHOEA-7) and with rituximab (RCHOEA-7), for patients with CD 20-positive non-Hodgkin's lymphoma.
Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. [2022]Rituximab is a chimeric monoclonal antibody directed against the B-cell CD20 antigen which has been utilized for therapy of B-cell non-Hodgkin's lymphoma (NHL). A previous clinical trial demonstrated that treatment with four weekly doses of 375 mg/m2 of Rituximab in patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma was well tolerated and had significant clinical activity.