Trial Outcomes & Findings for Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma (NCT NCT02541565)

Last Updated: 2020-10-14

Results Overview

The Primary Outcome measures toxicity, with particular attention to Events of Clinical Interest when adding MK-3475 to standard RCHOP therapy. The sample size of 30 patients will permit the estimation of a 40% incidence of grade 3-5 clinically relevant toxicity.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

Up to 90 days after completion of study treatment

Results posted on

2020-10-14

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Pembrolizumab, Combination Chemotherapy) Patients will receive pembrolizumab IV over 30 minutes on day 1 and prednisone PO on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Overall Study STARTED	30
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Pembrolizumab, Combination Chemotherapy) n=30 Participants Patients receive pembrolizumab IV over 30 minutes on day 1 and prednisone PO on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	26 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 90 days after completion of study treatment

Outcome measures

Outcome measures
Measure	Treatment (Pembrolizumab, Combination Chemotherapy) n=30 Participants Patients will receive pembrolizumab IV over 30 minutes on day 1 and prednisone PO on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Number of Participants With a Grade 3 or Higher Toxicity Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0	13 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Time from diagnosis until relapse or progression, non-protocol re-treatment of lymphoma, or death as a result of any cause, assessed up to 5 years

Statistical analysis will entail descriptive statistics, and survival analysis including Kaplan-Meier estimates, log-rank testing of univariate prognostic factors, Cox proportional hazards analysis, as well as T-testing and regression analysis for comparing continuous variables in correlative study data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Date of diagnosis to death from any cause, assessed up to 5 years

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 weeks after course 6

Tumor imaging at baseline and 4-6 weeks, +/-7 days, after 6 courses of induction therapy with MK-3475 + RCHOP to determine remission status. Response will be measured according to 2014 Criteria ("The Lugano Classification").

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to up to 5 years

Tissue-based assays for tumor and immune infiltrate will be conducted centrally when archival tissue is available. These analyses will seek to identify alterations in T-cell subsets for comparison with historical studies, and exploration of association with treatment outcomes achieved with study therapy.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Pembrolizumab, Combination Chemotherapy)

Serious events: 13 serious events

Other events: 19 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Pembrolizumab, Combination Chemotherapy) n=30 participants at risk Patients will receive pembrolizumab IV over 30 minutes on day 1 and prednisone PO on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Gastrointestinal disorders Upper GI Bleed	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Abdominal Pain	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Constipation	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Diarrhea	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Blood and lymphatic system disorders Febrile Neutropenia	13.3% 4/30 • Number of events 4 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
General disorders Fever	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Infections and infestations Infection-RSV	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Respiratory, thoracic and mediastinal disorders Pneumonitis	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
General disorders Rigors	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Cardiac disorders Worsening Systolic Function	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.

Other adverse events

Other adverse events
Measure	Treatment (Pembrolizumab, Combination Chemotherapy) n=30 participants at risk Patients will receive pembrolizumab IV over 30 minutes on day 1 and prednisone PO on days 1-5. Patients also receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine sulfate IV on day 2 of course 1 and on day 1 of subsequent courses. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Cyclophosphamide: Given IV Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV Prednisone: Given PO Rituximab: Given IV Vincristine Sulfate: Given IV
Blood and lymphatic system disorders Febrile Neutropenia	10.0% 3/30 • Number of events 4 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Nervous system disorders Syncope	10.0% 3/30 • Number of events 3 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Infections and infestations Infection	23.3% 7/30 • Number of events 9 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Skin and subcutaneous tissue disorders Rash	30.0% 9/30 • Number of events 9 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolis	3.3% 1/30 • Number of events 1 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Blood and lymphatic system disorders Anemia	3.3% 1/30 • Number of events 2 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
General disorders Fatigue	63.3% 19/30 • Number of events 22 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Nervous system disorders Sensory Neuropathy	56.7% 17/30 • Number of events 23 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Respiratory, thoracic and mediastinal disorders Cough	46.7% 14/30 • Number of events 17 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Constipation	40.0% 12/30 • Number of events 12 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Nausea	43.3% 13/30 • Number of events 15 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 10/30 • Number of events 14 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Nervous system disorders Dysgeusia	30.0% 9/30 • Number of events 9 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Diarrhea	30.0% 9/30 • Number of events 9 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Abdominal Pain	30.0% 9/30 • Number of events 10 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Nervous system disorders Headache	30.0% 9/30 • Number of events 10 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
General disorders Fever	23.3% 7/30 • Number of events 10 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Nervous system disorders Dizziness	23.3% 7/30 • Number of events 7 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Metabolism and nutrition disorders Anorexia	16.7% 5/30 • Number of events 5 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Mucositis	16.7% 5/30 • Number of events 5 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Musculoskeletal and connective tissue disorders Back Pain	16.7% 5/30 • Number of events 5 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Psychiatric disorders Insomnia	16.7% 5/30 • Number of events 5 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Dry Mouth	13.3% 4/30 • Number of events 4 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.
Gastrointestinal disorders Vomiting	13.3% 4/30 • Number of events 4 • Adverse events were collected from the time the consent form was signed though 90 days following cessation of MK-3475 treatment.

Additional Information

Dr. Stephen Smith

University of Washington

Phone: 206-606-6546

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place