RECRUITING

PACIFIC: Primary Mediastinal Large B-cell Lymphoma Treated with Antibody Therapy, Checkpoint Inhibitor in Frontline with ImmunoChemotherapy

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Conditions

Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell LymphomaAnn Arbor Stage II Primary Mediastinal (Thymic) Large B-Cell LymphomaAnn Arbor Stage III Primary Mediastinal (Thymic) Large B-Cell LymphomaAnn Arbor Stage IV Primary Mediastinal (Thymic) Large B-Cell LymphomaPrimary Mediastinal Large B-cell LymphomaBrentuximab VedotinNivolumabRituximabCyclophosphamideDoxorubicinPrednisone

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase II Study to Determine the Response Kinetics, Safety, and Efficacy of Brentuximab Vedotin and Nivolumab Alone and Then Combined with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone for Patients with Untreated Primary Mediastinal Large B-Cell Lymphoma

Quick Facts

Study Start:2021-05-10
Study Completion:2025-08-03
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04745949

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Histopathologically confirmed diagnosis of PMBL
  2. * Require a CD30 expression level of 1% or greater in the tumor or tumor-infiltrating lymphocytes by local immunohistochemistry
  3. * No prior treatment except
  4. * A prior limited-field radiotherapy
  5. * 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
  6. * Stage of patients: Stages II, III, IV, and stage I \>= 5 cm in the greatest dimension
  7. * 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
  8. * Age \>= 18 years at the time of signing the informed consent
  9. * Patients must have bi-dimensional measurable disease, as defined as radiographically apparent disease with the longest dimension of \>= 1.5 cm
  10. * 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)
  11. * Serum bilirubin \< 1.5 x ULN except in patients with Gilbert's syndrome as defined by \> 80% unconjugated bilirubin
  12. * 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
  13. * 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
  14. * Platelets \> 1000/mm\^3 unless deemed related to lymphoma involvement in the bone marrow and felt potentially reversible by the treating physician
  15. * Calculated creatinine clearance \>= 30 ml/min by Cockcroft-Gault formula
  16. * Patients must be willing to receive transfusions of blood products
  17. * Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening
  18. * 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
  1. * Patients with an urgent need for cytoreductive treatment will be excluded
  2. * 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
  3. * 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
  4. * Pregnant or lactating females
  5. * Known hypersensitivity to brentuximab vedotin, nivolumab, rituximab, doxorubicin, cyclophosphamide, or prednisone
  6. * Known human immunodeficiency virus (HIV) infection with active viremia
  7. * Patient with known HIV infection can be included if undetectable viral load, CD4 \>= 300 cells/microL and on HAART (highly active antiretroviral therapy)
  8. * Patients with active viremia of hepatitis B infection
  9. * Not including patients with prior hepatitis B vaccination; or positive serum hepatitis B antibody
  10. * Patients with active viremia of hepatitis C infection
  11. * Known hepatitis C infection is allowed as long as there is no active disease and is cleared by gastrointestinal (GI) consultation
  12. * All patients with central nervous system involvement with lymphoma
  13. * 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
  14. * Significant neuropathy (grades 2 or grade 1 with pain) within 14 days prior to enrollment
  15. * 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
  16. * Major surgery within 4 weeks of study entry or wound that is not healed from prior surgery or trauma
  17. * History of stroke or intracranial hemorrhage within 6 months prior to study entry
  18. * Vaccinated with live, attenuated vaccines within 4 weeks of study entry

Contacts and Locations

Study Contact

Ranjit Nair
CONTACT
(281) 787-7904
Rnair@mdanderson.org
Ranjit Nair
CONTACT
(281) 787-7904

Principal Investigator

Ranjit Nair
PRINCIPAL_INVESTIGATOR
M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center
Houston, Texas, 77030
United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

  • Ranjit Nair, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-05-10
Study Completion Date2025-08-03

Study Record Updates

Study Start Date2021-05-10
Study Completion Date2025-08-03

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

  • 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