Pembrolizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Diffuse Large B-cell Lymphoma or Grade 3b Follicular Lymphoma
Condition: Composite Lymphoma; Grade 3b Follicular Lymphoma; Stage I Diffuse Large B-Cell Lymphoma; Stage I Follicular Lymphoma; Stage II Diffuse Large B-Cell Lymphoma; Stage II Follicular Lymphoma; Stage III Diffuse Large B-Cell Lymphoma; Stage III Follicular Lymphoma; Stage IV Diffuse Large B-Cell Lymphoma; Stage IV Follicular Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Composite Lymphoma
Intervention: Cyclophosphamide; Doxorubicin Hydrochloride; Laboratory Biomarker Analysis; Pembrolizumab; Prednisone; Rituximab; Vincristine Sulfate
Intervention description: Given IV; Given IV; Correlative studies; Given IV; Given PO; Given IV; Given IV
Intervention MeSH terms: Prednisone; Cortisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Pembrolizumab; Vincristine; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This pilot phase I trial studies the side effects of pembrolizumab and combination
      chemotherapy in treating patients with previously untreated diffuse large B-cell lymphoma or
      grade 3b follicular lymphoma. Monoclonal antibodies, such as pembrolizumab and rituximab, may
      interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy,
      such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone,
      work in different ways to stop the growth of cancer cells, either by killing the cells, by
      stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab
      together with combination chemotherapy may be with a better treatment for diffuse large
      B-cell lymphoma or follicular lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously untreated diffuse large B-cell lymphoma or grade 3B follicular lymphoma (of
             any stage); subjects must be planned to receive full course (6 cycles) of RCHOP
             chemoimmunotherapy as per clinical standard of care; patients may have de novo DLBCL,
             and /or any of the following:

               -  Composite lymphomas, which include both diffuse DLBCL and another histology (most
                  commonly follicular lymphoma) in the same lymph node

               -  Transformed lymphoma with DLBCL histology, as long as the patient has not
                  received prior therapy for lymphoma

               -  Discordant presentations, such as DLBCL in a lymph node and low-grade lymphoma
                  such as follicular lymphoma in the bone marrow

          -  Be willing and able to provide written informed consent/assent for the trial

          -  Have measurable nodal disease, including at least 1 disease site measuring 1.5 cm in
             longest dimension on computed tomography (CT) or fludeoxyglucose (FDG)-positron
             emission tomography (PET)

          -  Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale (PS)

          -  Absolute neutrophil count (ANC) >= 1,500/mcL except in cases of marrow infiltration by
             lymphoma

          -  Platelets >= 100,000/mcL except in cases of marrow infiltration by lymphoma

          -  Hemoglobin >= 9 g/dL or >= 5.6 mmol/L except in cases of marrow infiltration by
             lymphoma

          -  Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated
             creatinine clearance >= 60 ml/min for subject with creatinine levels > 1.5 X
             institutional ULN (glomerular filtration rate [GFR] can also be used in place of
             creatinine or creatinine clearance [CrCl])

          -  Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total
             bilirubin levels > 1.5 ULN

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 X ULN or =< 5 X ULN for subjects with liver metastases

          -  International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless
             subject is receiving anticoagulant therapy; as long as PT or partial thromboplastin
             time (PTT) is within therapeutic range of intended use of anticoagulants; activated
             partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving
             anticoagulant therapy; as long as PT or PTT is within therapeutic range of intended
             use of anticoagulants, or subject is shown to have an antiphospholipid antibody on
             workup

          -  Female subject of childbearing potential should have a negative urine or serum
             pregnancy within 72 hours prior to receiving the first dose of study medication; if
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
             will be required

          -  Female subjects of childbearing potential should be willing to use 2 methods of birth
             control or be surgically sterile, or abstain from heterosexual activity for the course
             of the study through 120 days after the last dose of study medication; subjects of
             childbearing potential are those who have not been surgically sterilized or have not
             been free from menses for > 1 year

          -  Male subjects should agree to use an adequate method of barrier contraception starting
             with the first dose of study therapy through 120 days after the last dose of study
             therapy

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study drug or using an investigation 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

          -  Has a known additional malignancy that is progressing or requires active treatment;
             exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the
             skin, or in situ cervical cancer that has undergone potentially curative therapy

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis; subjects with previously treated brain metastases 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

          -  No active autoimmune disease that has required systemic treatment in 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 history of non-infectious pneumonitis that required steroids or current
             pneumonitis

          -  Has an active infection requiring intravenous antibiotic 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

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment

          -  Has received prior therapy with an anti-PD-1, anti-programmed cell death ligand 1
             (PD-L1), anti-programmed cell death ligand 2 (PD-L2), anti-tumor necrosis factor
             receptor superfamily, member 9 (CD137), or anti-cytotoxic T-lymphocyte-associated
             antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug
             specifically targeting T-cell co-stimulation or checkpoint pathways)

          -  Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Has known active hepatitis B (e.g., hepatitis B virus surface protein antigen [HBsAg]
             reactive or hepatitis B virus [HBV] deoxyribonucleic acid [DNA] detectable) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected)

          -  Has received a live vaccine within 30 days prior to the first dose of trial treatment