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Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell LymphomaPhase 2PACIFICNCT04745949

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

A Phase 2 study testing Brentuximab Vedotin, Cyclophosphamide and Doxorubicin in people with Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell Lymphoma and Ann Arbor Stage II Primary Mediastinal (Thymic) Large B-Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Brentuximab Vedotin, Cyclophosphamide and Doxorubicin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
10 May 2021to 3 Aug 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ranjit Nair contact

(281) 787-7904

Rnair@mdanderson.org

Ranjit Nair contact

(281) 787-7904

United States1 site, 1 recruiting

  • M D Anderson Cancer Center

    Houston, Texas, 77030

    Ranjit Nair, 281-787-7904, Rnair@mdanderson.org

    Ranjit Nair

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Evaluate the efficacy of primary mediastinal large B-cell lymphoma (PMBL) patients treated brentuximab vedotin (A) and nivolumab (O) alone and then combined with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP).

SECONDARY OBJECTIVE:

  1. Evaluate the antitumor activity, safety, tolerability, patient reported quality of life and survival of brentuximab vedotin and nivolumab (A-O) alone and then combined with R-CHP in patients with untreated PMBL.

EXPLORATORY OBJECTIVE:

  1. To evaluate the baseline and therapy induced changes in the profile of mutations and gene expression.

OUTLINE:

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. Brentuximab vedotin will be given intravenously (IV) over 30 minutes and nivolumab IV over 30 minutes on day 1. R-CHP: rituximab IV will be administered over 4-6 hours, cyclophosphamide IV over 1 hour, and doxorubicin IV over 1 hour on day 1, and prednisone orally (PO) once daily (QD) on days 1-5.

After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 4 months for 1 year.

Being tested
Brentuximab Vedotin, Cyclophosphamide, Doxorubicin, Nivolumab, Prednisone
Keywords
Primary Mediastinal Large B-cell Lymphoma, Brentuximab Vedotin, Nivolumab, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Brentuximab VedotinDrug

    Also called ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • DoxorubicinDrug

    Also called Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

    Given IV

  • NivolumabBiological

    Also called BMS-936558, CMAB819, MDX-1106, NIVO

    Given IV

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT04745949
Study groupRoleWhat they receive
Treatment (brentuximab vedotin, nivolumab, R-CHP)ExperimentalPatient 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.
Receives: Drug: Brentuximab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Biological: Nivolumab; Drug: Prednisone; Other: Quality-of-Life Assessment; Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Complete response rate

    Will be defined as the percentage of number of complete responses in total number of patients treated, which includes all the patients who were treated, even the patients dropped out at interim positron emission tomography/computed tomography scan after cycle 4 due to stable disease/progressive disease. Simon's optimal two-stage design will be used. Fisher's exact test will be used to evaluate the association between response and other categorical patient variables. T-test or Wilcoxon rank sum test will be used to evaluate the difference in continuous variables between responders and non-responders.

    Measured: At completion of therapy, assessed up to 2 years

Secondary outcomes (8)

  1. Overall response rate (complete response + partial response)

    Will monitor the overall response using the Bayesian stopping boundaries calculated based on beta-binomial distributions, and 95% confidence intervals will be calculated. Fisher's exact test will be used to evaluate the association between response and other categorical patient variables. T-test or Wilcoxon rank sum test will be used to evaluate the difference in continuous variables between responders and non-responders.

    Measured: Up to 2 cycles of brentuximab vedotin and nivolumab (1 cycle = 21 days)

  2. 1-year progression-free survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: From study entry to objective disease progression or death from any cause, whichever occurs first, assessed at 1 year

  3. 2 -year progression-free survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: From study entry to objective disease progression or death from any cause, whichever occurs first, assessed at 2 years

  4. 1-year overall survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: From study entry to death from any cause, assessed at 1 year

  5. 2-year overall survival

    Will be estimated using the method of Kaplan and Meier.

    Measured: From study entry to death from any cause, assessed at 2 years

  6. Duration of response

    Measured: Up to 2 years post-treatment

  7. Incidence of adverse events

    Will be summarized by frequency tables for all patients.

    Measured: Up to 100 days of the last dose of the study drug

  8. Health-related quality of life

    Will be assessed by the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire - Core (C) 30 (EORTC QLQ-C30).

    Measured: Up to 2 years post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Feb 2021
  2. Study start10 May 2021
  3. Primary completion3 Aug 2027 (estimated)
  4. Study completion3 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04745949
Sponsor's protocol ID
2020-0686
Other IDs
NCI-2020-13888, 2020-0686
Acronym
PACIFIC
Status last verified
Feb 2026
First submitted
4 Feb 2021
Last updated
19 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brentuximab Vedotin, Cyclophosphamide and Doxorubicin in people with Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell Lymphoma and Ann Arbor Stage II Primary Mediastinal (Thymic) Large B-Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ranjit Nair ((281) 787-7904, Rnair@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete response rate (time frame: At completion of therapy, assessed up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04745949.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2026.

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