This research study is studying several new investigational drug combinations as a possible treatment for follicular lymphoma. The drugs involved are: * Rituximab * Utomilumab * Avelumab * PF-04518600
This research study is a Phase 1 clinical trial. Phase 1 clinical trials test the safety of an investigational intervention and also try to define the appropriate dose of the investigational intervention to use for further studies. "Investigational" means that the intervention is being studied. Utomilumab and avelumab are drugs which may stimulate the immune system against tumor cells. Because they activate the immune system, they are sometimes called immunotherapy drugs. The FDA (the U.S. Food and Drug Administration) has not approved utomilumab or avelumab for treatment of this cancer. Rituximab is approved by the FDA (the U.S. Food and Drug Administration) as a treatment option for this disease. The purpose of this research is to learn about the effects of combining the immunotherapy drugs utomilumab and avelumab with rituximab in follicular lymphoma. The investigators hope to learn how safe the combinations of treatments are for participants with follicular lymphoma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Rituximab works by targeting the CD20 antigen on normal and malignant B-cells. Then the body's natural immune defenses are recruited to attack and kill the marked B-cells. Stem cells (young cells in the bone marrow that will develop into the various types of cells) do not have the CD20 antigen. This allows healthy B-cells to regenerate after treatment
Utomilumab is a drug which may stimulate the immune system against tumor cells. Because it activate the immune system, it is sometimes called immunotherapy drug
Avelumab is a drug which may stimulate the immune system against tumor cells. Because it activate the immune system, it is sometimes called immunotherapy drug
City of Hope
Duarte, California, United States
Yale New-Haven Hospital
New Haven, Connecticut, United States
Emory University
Atlanta, Georgia, United States
University of Chicago
Chicago, Illinois, United States
Recommended Phase 2 Dosing
Patients assessed for DLT after each 28-day cycle of treatment. Up to two cohorts of 3 patients per dose level plus expansion cohort. Rituximab/Utomilumab/Avelumab arm assessed 2 dose levels. Rituximab/Utomilumab/PF04518600 assessed 3 dose levels. Rituximab/PF04518600/Avelumab assessed 2 dose levels.
Time frame: 6 months total, assessed after each 28-day cycle
Number of Participants With Complete Response Per Lugano Criteria
Per 2014 Lugano criteria, a complete response is defined as PET-CT, score 1, 2, or 3\* with or without a residual mass on 5PS Or on CT, target nodes/nodal masses must regress to ≤ 1.5 cm in LDi, and no extralymphatic sites of disease
Time frame: Response assessed after completing treatment (6 months)
Number of Participants With Partial Response Per Lugano Criteria
Per 2014 Lugano criteria, partial response is defined as PET-CT Score 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size Or On CT ≥ 50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; no increase in non-measured lesions; spleen if enlarged must have regressed by \>50% in length beyond normal
Time frame: Response assessed after completing treatment (6 months)
Number of Participants With Objective Response Per Lugano Criteria
Objective response rate is defined as complete + partial response (CR + PR) Per 2014 Lugano criteria, CR is defined as PET-CT, score 1, 2, or 3\* with or without a residual mass on 5PS Or on CT, target nodes/nodal masses must regress to ≤ 1.5 cm in LDi, and no extralymphatic sites of disease Per 2014 Lugano criteria, PR is defined as PET-CT Score 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size. Or On CT ≥ 50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; no increase in non-measured lesions; spleen if enlarged must have regressed by \>50% in length beyond normal
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In the presence of tumor-associated antigens (TAAs), this may promote a T-cell-mediated immune response against TAA-expressing tumor cells. OX40
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Washington University in St. Louis
St Louis, Missouri, United States
Time frame: Response assessed after completing treatment (6 months)
Number of Participants With Objective Response Per LYRIC Criteria
Objective response rate is defined as complete + partial response (CR + PR) Per LYRIC criteria, CR is defined as PET-CT, score 1, 2, or 3\* with or without a residual mass on 5PS Or on CT, target nodes/nodal masses must regress to ≤ 1.5 cm in LDi, and no extralymphatic sites of disease Per LYRIC criteria, PR is defined as PET-CT Score 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size. Or On CT ≥ 50% decrease in SPD of up to 6 target measurable nodes and extranodal sites; no increase in non-measured lesions; spleen if enlarged must have regressed by \>50% in length beyond normal
Time frame: Response assessed after completing treatment (6 months)
Number of Participants With Complete Response Per LYRIC Criteria
Per LYRIC criteria, complete response is defined as PET-CT, score 1, 2, or 3\* with or without a residual mass on 5PS Or on CT, target nodes/nodal masses must regress to ≤ 1.5 cm in LDi, and no extralymphatic sites of disease
Time frame: Response assessed after completing treatment (6 months)
Progression-Free Survival Per Lugano Criteria
Time from registration until earlier of progression (Lugano criteria) or death from any cause, censored at date last known alive and progression-free
Time frame: 6 cycles (approximately 6 months) of treatment followed by 24 months of active follow-up with contact every 3 months
Progression-Free Survival Per LYRIC Criteria
Time from registration until earlier of progression (LYRIC criteria) or death from any cause, censored at date last known alive and progression-free
Time frame: 6 cycles (approximately 6 months) of treatment followed by 24 months of active follow-up with contact every 3 months
Overall Survival
Time from registration until death from any cause, censored at date last known alive
Time frame: 6 cycles (approximately 6 months) of treatment followed by 24 months of active follow-up with contact every 3 months followed by 3-year survival follow-up with contact every 6 months
Number of Participants With Grade 3 and Higher Toxicities
Number of patients who experience any adverse event with grade 3 or higher regardless of attribution to one or more study treatments
Time frame: 6 cycles (approximately 6 months) of treatment
Number of Participants With Grade 3 and Higher Related Toxicities
Number of patients who experience any adverse event with grade 3 or higher related to one or more study treatments
Time frame: 6 cycles (approximately 6 months) of treatment
Number of Participants With Grade 2 or Higher Toxicity
Number of patients who experience any adverse event with grade 2 or higher regardless of treatment attribution
Time frame: 6 cycles (approximately 6 months) of treatment followed