Recruiting

Phase 2

Antibody Therapy & Checkpoint InhibitorPACIFIC: Primary Mediastinal Large B-cell Lymphoma Treated With Antibody Therapy, Checkpoint Inhibitor in Frontline With ImmunoChemotherapy

Sponsor:

M.D. Anderson Cancer Center

Code:

NCT04745949

Conditions

Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Ann Arbor Stage II Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Ann Arbor Stage III Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Ann Arbor Stage IV Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Brentuximab Vedotin

Cyclophosphamide

Doxorubicin

Nivolumab

Prednisone

Study Details

Brief summary:

This phase II trial studies the effect of brentuximab vedotin and nivolumab alone and in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone in treating patients with untreated, stage I-IV primary mediastinal large B-cell lymphoma. Brentuximab vedotin is a monoclonal antibody, called brentuximab, linked to a toxic agent, called vedotin. Brentuximab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD30 receptors, and delivers vedotin to kill them. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Rituximab is a type of antibody therapy, which targets and attaches to the CD20 protein found on the surface of blood cells with cancer and some healthy blood cells. Chemotherapy drugs, such as cyclophosphamide, and doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells, or by stopping them from dividing. Prednisone is a steroid, a hormone (chemical messengers) with multiple roles, notably in the immune system and inflammation reduction. Steroids are poisonous to lymphocytes (white blood cells from which lymphomas develop). Giving brentuximab vedotin and nivolumab in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone may help to control the disease and be a less harmful regimen than standard chemotherapy in patients with primary mediastinal large B-cell lymphoma.

Conditions

Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Ann Arbor Stage II Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Ann Arbor Stage III Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Ann Arbor Stage IV Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Study ID

NCT04745949

Start date

May 10, 2021

Status verified date

Feb, 2026

Completion date

Aug 3, 2027

Anticipated

Primary completion date

Aug 3, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Histopathologically confirmed diagnosis of PMBL

Require a CD30 expression level of 1% or greater in the tumor or tumor-infiltrating lymphocytes by local immunohistochemistry
No prior treatment except

A prior limited-field radiotherapy
A short course (up to 7 days) of glucocorticoids =< 100 mg daily of prednisone equivalent which must cease prior to day 1 of cycle 1
Stage of patients: Stages II, III, IV, and stage I >= 5 cm in the greatest dimension
Patient or durable power of attorney (DPA) for healthcare must be able to understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form
Age >= 18 years at the time of signing the informed consent
Patients must have bi-dimensional measurable disease, as defined as radiographically apparent disease with the longest dimension of >= 1.5 cm
Patients with performance status of =< 3 (3 only allowed if decline in status is deemed related to lymphoma and felt potentially reversible by the treating physician)
Serum bilirubin < 1.5 x ULN except in patients with Gilbert's syndrome as defined by > 80% unconjugated bilirubin
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =< 3 x ULN or < 5 x ULN if hepatic metastases are present
Absolute neutrophil count (ANC) > 1000/mm\^3 unless deemed related to lymphoma involvement in the bone marrow and felt potentially reversible by the treating physician
Platelets > 1000/mm\^3 unless deemed related to lymphoma involvement in the bone marrow and felt potentially reversible by the treating physician
Calculated creatinine clearance >= 30 ml/min by Cockcroft-Gault formula
Patients must be willing to receive transfusions of blood products
Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening
Women of childbearing potential and men who are sexually active with a woman of childbearing potential must be practicing a highly effective method of birth control during and after the study (12 months for women and 3 months for men), consistent with local regulations regarding the use of birth control methods for subjects participating in this clinical study. Men must agree to not donate sperm during and for up to 3 months after their conclusion of therapy on study. For females, these restrictions apply for 1 month after the last dose of study drug

Exclusion Criteria:

Patients with an urgent need for cytoreductive treatment will be excluded
Any serious medical condition including but not limited to uncontrolled hypertension, uncontrolled congestive heart failure within past 6 months prior to screening (class 3 \[moderate\] or class 4 \[severe\] cardiac disease as defined by the New York Heart Association Functional Classification), uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary disease (COPD), left ventricular ejection fraction (LVEF) less than 40%, renal failure, active infection, history of invasive fungal infection, moderate to severe hepatic disease (Child Pugh class B or C), active hemorrhage, laboratory abnormality, or psychiatric illness that, in the investigators opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form. Patients with history of cardiac arrhythmias should have cardiac evaluation and clearance
Previous anthracycline exposure with expected lifetime exposure to doxorubicin > 450 mg/m\^2, considering the planned anthracycline exposure in this study with potential six cycles of R-CHP
Pregnant or lactating females
Known hypersensitivity to brentuximab vedotin, nivolumab, rituximab, doxorubicin, cyclophosphamide, or prednisone
Known human immunodeficiency virus (HIV) infection with active viremia

Patient with known HIV infection can be included if undetectable viral load, CD4 >= 300 cells/microL and on HAART (highly active antiretroviral therapy)
Patients with active viremia of hepatitis B infection

Not including patients with prior hepatitis B vaccination; or positive serum hepatitis B antibody
Patients with active viremia of hepatitis C infection

Known hepatitis C infection is allowed as long as there is no active disease and is cleared by gastrointestinal (GI) consultation
All patients with central nervous system involvement with lymphoma
Diagnosis of prior malignancy within the past 2 years with the exception of successfully treated basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast. History of other malignancies are allowed if in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy > 3 years
Significant neuropathy (grades 2 or grade 1 with pain) within 14 days prior to enrollment
Contraindication to any of the required concomitant drugs or supportive treatments or intolerance to hydration due to preexisting pulmonary or cardiac impairment including pleural effusion requiring thoracentesis or ascites requiring paracentesis not due to lymphoma
Major surgery within 4 weeks of study entry or wound that is not healed from prior surgery or trauma
History of stroke or intracranial hemorrhage within 6 months prior to study entry
Vaccinated with live, attenuated vaccines within 4 weeks of study entry

Study Design

Enrollment

31 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment (brentuximab vedotin, nivolumab, R-CHP)

Patient will receive an immune lead-in of 2 cycles of Brentuximab vedotin and Nivolumab (A-O) (cycles 1 and 2), which has an appropriate futility rules in place to close early if efficacy targets are not met. At cycle 3 and 4, patients will receive A-O with R-CHP. Patients who will have achieved complete response (CR) at PET/CT before cycle 5 will receive 2 more cycles of A-O-R-CHP (cycle 5 and 6) and A-O only for cycle 7 and 8. If these patients still present CR at PET/CT after cycle 8, they will have completed therapy and will be followed up. In case of stable disease or progressive disease at PET/CT after cycle 4, the patient will be taken off the trial. Patients who present further response but no CR, at PET/CT before cycle 5 will receive 4 more cycles A-O-R-CHP (cycles 5-8). If they reach CR at PET/CT after cycle 8, they will have completed therapy and will be followed up. All patients will receive a total of 8 cycles of A-O. The cycle duration is 21 days.

Interventions

Brentuximab Vedotin

Given IV

Cyclophosphamide

Given IV

Doxorubicin

Given IV

Nivolumab

Given IV

Prednisone

Given PO

Quality-of-Life Assessment

Ancillary studies

Rituximab

Given IV

Primary outcome measure

Complete response rate [ Time Frame: At completion of therapy, assessed up to 2 years ]

Central Contacts and Locations

Central contacts

Ranjit Nair

(281) 787-7904 Rnair@mdanderson.org

Ranjit Nair

(281) 787-7904

Locations

M D Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Ranjit Nair

281-787-7904 Rnair@mdanderson.org

Principal Investigator:

Ranjit Nair

More Information

Sponsor

M.D. Anderson Cancer Center

Last update posted

Feb 19, 2026

Last verified

Feb, 2026

Keywords

Primary Mediastinal Large B-cell Lymphoma
Brentuximab Vedotin
Nivolumab
Rituximab
Cyclophosphamide
Doxorubicin
Prednisone

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by M.D. Anderson Cancer Center on 2026-02-19.