A Randomized Phase 3 Trial of Nivolumab (NSC# 748726) in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma

Plain English Summary

Nivolumab in Combination With Chemo-Immunotherapy for the Treatment of Newly Diagnosed Primary Mediastinal B-Cell Lymphoma is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Primary Mediastinal Large B-Cell Lymphoma. Tests nivolumab combined with chemo-immunotherapy to treat newly diagnosed Primary Mediastinal B-Cell Lymphoma (PMBCL). For patients aged 2 years and older with PMBCL, who are in good health or have mild symptoms related to the lymphoma. Participation involves regular check-ups, blood tests, and possible bone marrow tests. Treatment includes chemotherapy and nivolumab. Alternative treatments include standard chemo-immunotherapy without nivolumab. The trial aims to enroll 244 participants.

Official Summary

This phase III trial compares the effects of nivolumab with chemo-immunotherapy versus chemo-immunotherapy alone in treating patients with newly diagnosed primary mediastinal B-cell lymphoma (PMBCL). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Treatment for PMBCL involves chemotherapy combined with an immunotherapy called rituximab. Chemotherapy drugs work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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 nivolumab with chemo-immunotherapy may help treat patients with PMBCL.

Who Can Participate

Here is what you need to know about eligibility for this trial. Ages 2 years and older with PMBCL confirmed by biopsy. Good overall health or mild symptoms related to the lymphoma. Creatinine clearance of at least 30 mL/min for adults, or 70 mL/min/1.73 m² for children. No active heart disease, infections, or other serious health issues. This trial is studying Primary Mediastinal Large B-Cell Lymphoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures the time until the disease progresses, which is crucial for patients as it can help determine the effectiveness of the treatment. The specific primary outcome measures are: Progression-free survival (PFS) (From enrollment on the study to first occurrence of relapse/progression or death, assessed up to 7 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial aims to fill a treatment gap by exploring a new combination therapy for PMBCL, potentially offering better outcomes. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Primary Mediastinal Large B-Cell Lymphoma, where improved treatment options are needed.

Investor Insight

The market for lymphoma treatments is large, with this trial potentially leading to a new standard of care, making it an attractive investment opportunity. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have any heart or liver problems, as these may affect your eligibility. Participation involves regular check-ups, blood tests, and possible bone marrow tests. Treatment includes chemotherapy and nivolumab. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 244 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo blood and CSF sample collection
• PROCEDURE: Bone Marrow Aspiration — Undergo bone marrow biopsy and aspiration
• PROCEDURE: Bone Marrow Biopsy — Undergo bone marrow biopsy and aspiration
• PROCEDURE: Computed Tomography — Undergo CT or PET/CT
• DRUG: Cyclophosphamide — Given IV

Primary Outcomes

• Progression-free survival (PFS) (From enrollment on the study to first occurrence of relapse/progression or death, assessed up to 7 years)

Secondary Outcomes

• Efficacy-related event-free survival (Up to 7 years)
• Therapy-related event-free survival (Up to 7 years)
• Overall survival (Up to 7 years)
• Proportion of positive positron emission tomography (PET) scans (Up to 6 cycle (1 cycle = 21 days))

Full Eligibility Criteria

Inclusion Criteria:

* Age \>= 2 years
* Patient must have histologically confirmed primary mediastinal B-cell lymphoma (PMBCL) as defined by World Health Organization (WHO) criteria
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 or ECOG performance status of 3 if poor performance is related to lymphoma

  * Children's Oncology Group (COG) Institutions: Use Karnofsky for patients \>= 17 and \< 18 years of age and Lansky for patients \< 17 years of age
* Adults (age 18 or older): Creatinine clearance \>= 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
* Pediatric Patients (age \< 18 years): The following must have been obtained within 14 days prior to registration:

  * Measured or calculated (based on institutional standard) creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 ml/min/1.73 m\^2, or
  * Serum creatinine =\< 1.5 x institutional upper limit of normal (IULN), or a serum creatinine based on age/sex as follows:

    * Age : 2 to \< 6 year; Maximum serum creatinine (mg/dL): 0.8 (male; 0.8 (female)
    * Age : 6 to \< 10 years; Maximum serum creatinine (mg/dL): 1 (male); 1 (female)
    * Age : 10 to \< 13 years; Maximum serum creatinine (mg/dL): 1.2 (male); 1.2 (female)
    * Age : 13 to \< 16 years; Maximum serum creatinine (mg/dL): 1.5 (male); 1.4 (female)
    * Age : \>= 16 years to \< 18 years; Maximum serum creatinine (mg/dL): 1.7 (male); 1.4 (female)
* Patients with abnormal liver function will be eligible to enroll if the lab abnormality is thought to be due to the lymphoma or Gilbert's syndrome
* Age \>= 18 years: Ejection fraction of \>= 50% by echocardiogram
* Age \< 18 years: Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

* Administration of prior anti-cancer therapy except as outlined below:

  * A short course (=\< 2 weeks) of corticosteroids for the relief of lymphoma-related symptoms
  * A single course of COP (cyclophosphamide, vincristine, and prednisone)
  * One cycle of chemo-immunotherapy including R-CHOP, DA-EPOCH-R, a pediatric mature B-cell non-Hodgkin lymphoma (B-NHL) induction therapy (such as ANHL1131), or intrathecal chemotherapy that has not started more than 21 days prior to enrollment
* Active ischemic heart disease or heart failure
* Active uncontrolled infection
* Central nervous system (CNS) involvement of lymphoma
* Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of this trial
* Active autoimmune disease that has required systemic treatment (such as disease modifying agents, corticosteroids, or immunosuppressive agents) in the past 2 years. Replacement therapy such as thyroxine, insulin or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment
* In patients \< 18 years of age hepatitis B serologies consistent with past or current infections
* Patients with severe hepatic impairment (Child-Pugh class C or serum total bilirubin \> 5.0 mg/dL) unless thought to be due to lymphoma or Gilbert's syndrome
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of \< 1% per year when used consistently and correctly) for the duration of their study participation
* Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last dose of rituximab

Trial Locations

• Children's Hospital of Alabama, Birmingham, Alabama, United States
• USA Health Strada Patient Care Center, Mobile, Alabama, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• Banner Children's at Desert, Mesa, Arizona, United States
• Banner University Medical Center - Tucson, Tucson, Arizona, United States
• Arkansas Children's Hospital, Little Rock, Arkansas, United States
• UC Irvine Health Cancer Center-Newport, Costa Mesa, California, United States
• Kaiser Permanente Downey Medical Center, Downey, California, United States
• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care, Irvine, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Primary Mediastinal Large B-Cell Lymphoma
• Lymphoma
• Immunotherapy
• Chemotherapy
• Cancer Treatment

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