Pembrolizumab in Combination With Chemotherapy for Patients With Untreated B Cell Lymphoma

NCT03995147 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB19-0072
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

This study will research untreated non-germinal center diffuse large B cell lymphoma and what causes the disease and the way patients respond to pembrolizumab combined with R-CHOP chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) therapy.

Conditions

B Cell Lymphoma; Lymphoma; Lymphoma, B-Cell; Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) rate when combining pembrolizumab with R-CHOP

  24 months

Secondary Outcomes (4)

• Complete response (CR) rate after 6 cycles of pembrolizumab in combination with R-CHOP

  18 weeks

• Event free survival (EFS) rate after 6 cycles of pembrolizumab in combination with R-CHOP

  18 weeks

• Overall survival (OS) rate after 6 cycles of pembrolizumab in combination with R-CHOP

  18 weeks

• Number of participants with treatment related adverse events as assessed by CTCAE v 4.0

  29 months

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Drug: Pembrolizumab; Drug: R-CHOP Protocol

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered at a fixed dose of 200mg intravenously every 3 weeks in combination with R-CHOP for 6 cycles. Participants that respond to the combination regiment will continue to receive pembrolizumab 200 mg IV every 3 weeks for additional 35 cycles (2 years).

Treatment Arm

R-CHOP Protocol DRUG

R-CHOP chemo-immunotherapy will be administered in combination with Pembrolizumab

Also known as: Rituximab, Cyclophosphamide, doxorubicin, vincristine, prednisone

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with a histologically confirmed diagnosis of diffuse large B cell lymphoma or high-grade B cell lymphoma of a non-germinal center phenotype according to Hans criteria are eligible for enrollment in this study.
• International Prognostic Index (IPI) score of ≥ 3, or an age-adjusted (aa) IPI score of ≥ 2.
• A male participant must agree to use a contraception during the treatment period and for at least 120 days after the final dose of study treatment and refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease with one or more measurable lymphoma lesions ( \>1.5 cm in the long axis and \>1.0 cm in the short axis).
• Patients must be able to provide an archived tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Have adequate organ function. See below for adequate organ function laboratory values:
• Hematological
• Absolute neutrophil count (ANC) less or equal to 1000/microliter
• Platelets less or equal to 100,000/microliters
• Hemoglobin less or equal to 8.0/grams per decilitre

You may not qualify if:

• Positive urine pregnancy test within 72 hours prior to the initiation of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
• Has received prior anti-lymphoma therapy, including radiation therapy, chemotherapy, targeted therapy, or immunotherapy.
• Note: Prior corticosteroid treatment (\<10 days in duration) to alleviate lymphoma-elated symptoms is permitted.
• Note: If participant received major surgery, he or she must have recovered adequately from complications from the intervention prior to starting study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent, with the exception of short-term corticosteroid use to control lymphoma-related symptoms as outlined above) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Other exceptions may be permitted after discussion with the principal investigator.
• Has known active CNS involvement by lymphoma.
• Has a diagnosis of high-grade B cell lymphoma with MYC and BCL2 and/or BCL6 gene rearrangements (double hit lymphoma), primary mediastinal lymphoma, gray zone lymphoma, composite lymphoma, or previously-untreated low-grade lymphoma with disease transformation to DLBCL.
• Has severe hypersensitivity (≥ grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• University of Chicago: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

pembrolizumab; R-CHOP protocol; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Justin Kline, MD

  University of Chicago Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2019
• First Posted: June 21, 2019
• Study Start: August 29, 2019
• Primary Completion (Estimated): February 20, 2027
• Study Completion (Estimated): February 20, 2027
• Last Updated: June 8, 2025

Record last verified: 2025-06

Locations

US (1)