CC-99282 + Rituximab for Non-Hodgkin's Lymphoma

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nathan Denlinger

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Pregnancy, Breastfeeding, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 265

Duration: 24 months

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for individuals with non-Hodgkin's lymphoma who haven't responded well to CAR-T cell therapy. It evaluates the safety and effectiveness of using CC-99282, a drug that may enhance the immune system, alongside rituximab, which targets cancer cells. The trial aims to determine the optimal dose and assess how well this combination combats cancer. Suitable participants have non-Hodgkin's lymphoma, have undergone CAR-T therapy, and have not achieved the desired response. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that rituximab is generally well-tolerated and has treated non-Hodgkin's lymphoma for many years. Studies indicate that over 85% of patients experience some side effects, usually mild, such as fever and chills. Serious reactions, like skin problems, can occur but are rare.

In contrast, little information is available about CC-99282. This phase 1 trial means the treatment is still being tested for safety in humans. Phase 1 trials aim to find the right dose and check for any serious side effects. While rituximab's safety is well-known, researchers are still studying CC-99282 to understand its safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the combination of CC-99282 and rituximab for treating Non-Hodgkin's Lymphoma because this treatment introduces a novel mechanism of action. Unlike traditional therapies that primarily target the CD20 protein on B cells, CC-99282 is an oral drug that works by modulating the immune system, potentially enhancing the body's ability to fight cancer cells more effectively. This dual approach not only leverages rituximab's established efficacy in targeting specific cancer cells but also adds a new, complementary strategy that could improve patient outcomes. Additionally, the oral administration of CC-99282 offers a convenient option compared to more invasive treatments, which could improve patient compliance and quality of life.

What evidence suggests that CC-99282 and rituximab might be an effective treatment for non-Hodgkin's lymphoma?

In this trial, participants will receive a combination of rituximab and CC-99282. Research has shown that rituximab effectively treats B-cell non-Hodgkin's lymphoma, with studies indicating a 92% overall response rate. Rituximab works by attaching to a protein called CD20 on cancer cells, aiding the immune system in destroying them. CC-99282, a newer treatment, is under study for its potential to harness the body's immune system to fight cancer. It aims to stop tumor cells from growing and spreading. Although detailed information on CC-99282's effectiveness in humans remains limited, it is designed to boost the immune response against cancer. Using these treatments together could offer a promising option for patients who haven't fully responded to other therapies. ^{1 2 4 5 6}

Who Is on the Research Team?

Nathan Denlinger, DO, MS

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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

Aspartate aminotransferase (AST) ≤ 3.0 × ULN (obtained within 14 days prior to initiating study treatment)

Females of childbearing potential must have a negative serum pregnancy test within 3 days prior to enrollment. Pregnancy tests must be medically supervised with a minimum sensitivity of 25mIU/ml. NOTE: a female of childbearing potential is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months, i.e. has had menses at any time in the preceding 24 consecutive months. Documentation of postmenopausal status must be provided. Further information on pregnancy testing and the definition of a female of childbearing potential located in the CC-99282 pregnancy prevention plan document

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• CC-99282
• Rituximab

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (rituximab, CC-99282) Experimental Treatment 6 Interventions

Patients receive rituximab intravenously (IV) on day 1 of each cycle and CC-99282 orally (PO) once daily (QD) on days 1-14 of each cycle. Treatment repeats every 28 days for up to 6 cycles of rituximab and up to 26 cycles of CC-99282 in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (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

Who Is Running the Clinical Trial?

Nathan Denlinger

Lead Sponsor

Trials

1

Recruited

20+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Rituximab, the first monoclonal antibody approved for cancer treatment, has been administered to approximately 36,000 patients, showing efficacy in treating relapsed or refractory CD20+ low-grade non-Hodgkin's lymphoma.

Serious infusion-related reactions, including cardiopulmonary issues and tumor lysis syndrome, occur in a small percentage of patients (0.04% to 0.07%), with higher risks in those with many circulating malignant cells or pre-existing cardiovascular conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the use of rituximab for treatment of B-cell non-Hodgkin's lymphoma: a benefit-risk update. Kunkel, L., Wong, A., Maneatis, T., et al.[2022]

Rituximab has been shown to significantly improve progression-free and overall survival in patients with non-Hodgkin's lymphoma, based on a systematic review of 23 randomized controlled trials.

The treatment is particularly effective when added to chemotherapy for aggressive B-cell lymphomas and for both initial and subsequent treatments of indolent B-cell lymphomas, as well as for maintenance therapy in responding patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in lymphoma: a systematic review and consensus practice guideline from Cancer Care Ontario. Cheung, MC., Haynes, AE., Meyer, RM., et al.[2018]

In a study involving four patients with primary refractory or early relapsed T cell rich B cell lymphomas (TCRBCL), the combination of rituximab with chemotherapy (vinorelbine and gemcitabine) resulted in three complete responses and one partial response, demonstrating significant efficacy.

The treatment was well-tolerated, with no significant adverse effects reported, suggesting that rituximab combined with chemotherapy could be a promising option for treating TCRBCL and warrants further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab in combination with vinorelbine/gemcitabine chemotherapy in patients with primary refractory or early relapsed T cell rich B cell lymphoma. A pilot study. Xiros, N., Economopoulos, T., Valsami, S., et al.[2022]

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown to induce responses in nearly 50% of patients with relapsed follicular/low-grade non-Hodgkin's lymphoma, with complete remissions occurring in 6% of cases, highlighting its efficacy in treating this type of cancer.

The drug is generally well tolerated, with common side effects being mild to moderate fevers and chills, and it is also effective against various other B-cell malignancies, suggesting its potential for broader applications in both cancer treatment and autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: clinical development and future directions. Cheson, BD.[2019]

Rituximab, when added to standard chemotherapy, significantly improved survival rates in patients with non-Hodgkin's lymphoma.

In patients with chronic B-cell lymphocytic leukemia, the addition of rituximab to fludarabine-based regimens enhanced both response rates and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of the safety and feasibility of rapid infusion of rituximab. Atmar, J.[2022]

Rituximab is the first FDA-approved monoclonal antibody for cancer treatment, specifically targeting the CD20 antigen on B cells, and has shown efficacy in treating relapsed low-grade and follicular non-Hodgkin's lymphoma in multicenter studies.

The treatment is generally well-tolerated, with side effects mainly consisting of mild fevers and chills during the first infusion, and its low immunogenicity allows for potential future treatments without significant complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of rituximab, the new FDA-approved antibody. Leget, GA., Czuczman, MS.[2019]

In a phase II study involving 37 patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, Rituximab was found to be well tolerated, with most adverse events being mild and decreasing with subsequent infusions.

The treatment resulted in a 57% overall response rate, with 14% achieving a complete response and 43% a partial response, indicating significant clinical activity and suggesting that extended Rituximab treatment may be effective for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended Rituximab (anti-CD20 monoclonal antibody) therapy for relapsed or refractory low-grade or follicular non-Hodgkin's lymphoma. Piro, LD., White, CA., Grillo-López, AJ., et al.[2022]

In a phase II trial involving 123 patients with advanced indolent lymphoma, the combination of interferon-alpha2a (IFN) with extended dosing of rituximab significantly improved response rates, with 94% of patients achieving an overall response compared to 78% with rituximab alone.

The addition of IFN not only increased the number of patients achieving complete responses (CR) but also helped maintain these responses for over 24 months in 72% of patients, indicating that this combination therapy can lead to long-term benefits without the need for chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Kimby, E., Jurlander, J., Geisler, C., et al.[2021]

Rituximab was the first monoclonal antibody approved for cancer therapy and has significantly improved survival rates in patients with diffuse large cell lymphoma when combined with CHOP chemotherapy.

Initially approved in 1997 for relapsed or refractory low-grade or follicular, CD20-positive, B-cell non-Hodgkin's lymphoma, rituximab is also being researched for other B-cell malignancies and nonmalignant diseases like autoimmune disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab: review and clinical applications focusing on non-Hodgkin's lymphoma. King, KM., Younes, A.[2015]

In a study of 40 patients with low-grade or follicular B-cell non-Hodgkin's lymphoma, the combination of Rituxan (Rituximab) and CHOP chemotherapy resulted in a high overall response rate of 95%, with 55% achieving complete remission.

The combination therapy showed promising safety, with common side effects being manageable, and it also indicated potential for clearing minimal residual disease, as evidenced by the conversion of the bcl-2 translocation from positive to negative in several patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. Czuczman, MS., Grillo-López, AJ., White, CA., et al.[2022]

Citations

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Epcoritamab (GEN3013; DuoBody-CD3×CD20) to induce ... Epcoritamab is a novel subcutaneously administered bsAb with a favorable safety profile and encouraging preliminary anti-tumor activity at low doses.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.8009

Epcoritamab (GEN3013; DuoBody-CD3×CD20) to induce ... Epcoritamab is a novel subcutaneously administered bsAb with a favorable safety profile and encouraging preliminary anti-tumor activity at low doses.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04663347

NCT04663347 | Safety and Efficacy Trial of Epcoritamab ... The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, ...

4. news.abbvie.com news.abbvie.com/2024-12-07-Investigational-Epcoritamab-DuoBody-R-CD3xCD20-Combination-Therapy-Shows-High-Response-Rates-in-Clinical-Trial-of-Patients-With-Relapsed-or-Refractory-R-R-Follicular-Lymphoma-FL

Investigational Epcoritamab (DuoBody® CD3xCD20) ... These data highlight the potential benefits of epcoritamab in treating patients with relapsed or refractory follicular lymphoma.

5. ir.genmab.com ir.genmab.com/news-releases/news-release-details/epkinlyr-epcoritamab-bysp-approved-us-fda-patients-relapsed-or

EPKINLY® (epcoritamab-bysp) Approved by U.S. FDA for ... EPKINLY is a prescription medicine used to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03625037

Study Details | NCT03625037 | First-in-Human (FIH) Trial ... The purpose of this trial is to measure the following in participants with relapsed and/or refractory B-cell lymphoma who receive epcoritamab.