Pembrolizumab With Rituximab or Obinutuzumab in Treating Patients With Relapsed or Refractory Follicular Lymphoma or Diffuse Large B Cell Lymphoma

NCT03401853 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 9469NCI-2017-02361RG1717070
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pembrolizumab with rituximab or obinutuzumab work in treating patients with follicular lymphoma or diffuse large B cell lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Rituximab and obinutuzumab are monoclonal antibodies. They bind 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 pembrolizumab with rituximab or obinutuzumab may help kill more cancer cells in patients with follicular lymphoma or diffuse large B cell lymphoma.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma

Keywords

Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Will be defined as the rate of complete + partial responses using computed tomography (CT) criteria (Lugano 2014).

  Up to 90 days after the last dose of pembrolizumab

Secondary Outcomes (3)

• Incidence of Serious or Drug-related Adverse Events

  Up to 90 days after the last dose of pembrolizumab

• Progression-free Survival (PFS)

  Up to 90 days after the last dose of pembrolizumab

• Overall Survival (OS)

  Up to 90 days after the last dose of pembrolizumab

Study Arms (3)

Arm I (pembrolizumab, rituximab)

EXPERIMENTAL

INDUCTION: Patients diagnosed with R/R FL receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, and 15 of cycle 1, and on day 1 of cycle 2. EXTENDED THERAPY: Patients with at least a partial response receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years (35 cycles) in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Rituximab

Arm II (pembrolizumab, rituximab)

EXPERIMENTAL

INDUCTION: Patients diagnosed with R/R DLBCL receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 1, 8, and 15 of cycle 1, and on day 1 of cycle 2. EXTENDED THERAPY: Patients with at least a partial response receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years (35 cycles) in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Rituximab

Arm III (pembrolizumab, obinutuzumab)

EXPERIMENTAL

INDUCTION: Patients diagnosed with R/R FL receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive obinutuzumab IV on days 1, 8, and 15 of cycle 1, and on day 1 of cycle 2. EXTENDED THERAPY: Patients with at least a partial response receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for up to 2 years (35 cycles) in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Obinutuzumab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (pembrolizumab, rituximab); Arm II (pembrolizumab, rituximab); Arm III (pembrolizumab, obinutuzumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm I (pembrolizumab, rituximab); Arm II (pembrolizumab, rituximab); Arm III (pembrolizumab, obinutuzumab)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83, rituximab biosimilar TQB2303, rituximab-abbs, Truxima, Rituximab Biosimilar SIBP-02

Arm I (pembrolizumab, rituximab); Arm II (pembrolizumab, rituximab)

Obinutuzumab BIOLOGICAL

Given IV

Also known as: Anti-CD20 Monoclonal Antibody R7159, GA-101, GA101, Gazyva, huMAB(CD20), R7159, RO 5072759, RO-5072759, RO5072759

Arm III (pembrolizumab, obinutuzumab)

Eligibility Criteria

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

You may qualify if:

• Have relapsed/refractory DLBCL or relapsed/refractory FL
• For DLBCL, patients must have relapsed after, declined, or considered ineligible for high-dose chemotherapy and autologous stem cell transplantation
• For FL, in addition to relapsed/refractory disease status, patients must have received therapy with CD20 antibody-directed therapy, and must have an indication for treatment; FL eligibility also requires patients have no standard options with curative potential, nor options with more favorable risk/benefit ratio in the judgment of the investigator
• For FL Arm C (obinutuzumab + pembrolizumab), patients must have relapsed/refractory disease after rituximab-containing therapy including:
• Rituximab in combination with chemotherapy (at 1 prior line) or
• \>= 2 prior lines of therapy
• Patients may have no standard options with curative potential, nor options with more favorable risk/benefit ratio in the judgment of the investigator
• Be willing and able to provide written informed consent/assent for the trial
• Have measurable disease (1.5 cm or greater in the longest diameter of nodal or extranodal disease)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 500/uL (within 28 days of cycle 1 day 1)
• Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed
• No lower limit if cytopenia is related to bone marrow involvement
• Platelets \>= 25,000/uL (within 28 days of cycle 1 day 1)
• Growth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment, except for physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency which is permitted
• Has a known history of active TB (Bacillus tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• Prior allogeneic transplant, within the last 5 years
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to a previously administered agent
• \* Note: Subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• \* Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or lymphomatous meningitis; subjects with previously treated brain metastases or lymphomatous meningitis may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
• 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 (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has known history of, or any evidence of active, non-infectious pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator

Sponsors & Collaborators

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

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Non-Hodgkin

Interventions

pembrolizumab; Rituximab; CT-P10; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma; 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

Results Point of Contact

• Title: Stephen Smith, MD
• Organization: University of Washington

ssmith50@fredhutch.org

(206) 606-6546

Study Officials

• Stephen D. Smith

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 10, 2018
• First Posted: January 17, 2018
• Study Start: March 23, 2018
• Primary Completion: December 19, 2023
• Study Completion: September 19, 2024
• Last Updated: July 22, 2025
• Results First Posted: April 18, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)