Umbralisib and Pembrolizumab in Treating Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
Condition: Hodgkin's Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: Pembrolizumab; Umbralisib
Intervention description: Given IV; Given PO
Intervention MeSH terms: Pembrolizumab; Immunoglobulins; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well umbralisib and pembrolizumab work in treating patients
      with classical Hodgkin lymphoma that has come back (relapsed) or does not respond to
      treatment (refractory). Umbralisib may stop the growth of cancer cells by blocking some of
      the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as
      pembrolizumab, may help the body's immune system attack the cancer, and may interfere with
      the ability of cancer cells to grow and spread. Giving umbralisib and pembrolizumab may work
      better in treating classical Hodgkin lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Relapsed or refractory CHL that has received at least 1 prior lines of therapy

          -  Measurable fludeoxyglucose F-18 (FDG)-avid disease defined by standard criteria
             (Lugano 2014) and a minimum of 1.0 cm in diameter

          -  Prior treatment with anti-PD1 or anti-PDL1 therapy is allowed.

             * Patients who are currently on anti-PD1 or anti-PDL1 therapy who have failed to
             achieve a CR after at least 18 weeks of treatment may enroll on study. For these
             patients, anti-PD1 or anti-PDL1 therapy may be delayed for screening and to align
             pembrolizumab dosing with the expected cycle 1 day 1. Patients with progressive
             disease after prior anti-PD1 or anti-PDL1 therapy do not have to be treated for 18
             weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Ability to swallow and retain oral medication

          -  Willingness and ability to comply with study and follow-up procedures, and give
             written informed consent

          -  Female subjects of childbearing potential must be surgically sterile, be
             post-menopausal (for at least 1 year prior to screening visit), or must have a
             negative pregnancy test within 3 days prior to cycle 1 day 1 and agree to use
             medically acceptable contraception throughout the study period and for 4 months after
             the last dose of either study drug. Men of reproductive potential may not participate
             unless they agree to use medically acceptable contraception throughout the study
             period and for 4 months after the last dose of either study drug

          -  Patients must be expected to receive at least 2 cycles of therapy

          -  Patients should have a life expectancy if untreated of >= 90 days in the opinion of
             the investigator

          -  Patients must have a FDG-positron emission tomography (PET)-computed tomography (CT)
             of chest, abdomen, and pelvis within 42 days of enrollment

          -  Absolute neutrophil count (ANC) > 750

          -  Platelet count > 40,000

          -  Total bilirubin =< 1.5 times the upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (if
             known liver involvement then =< 5 x ULN is allowed)

          -  Calculated creatinine clearance > 30 mL/min (as calculated by the Cockcroft-Gault
             formula)

        Exclusion Criteria:

          -  Patients receiving cancer therapy (i.e., chemotherapy, immunotherapy, biologic
             therapy, hormonal therapy, surgery and/or tumor embolization, prednisone > 10 mg or
             equivalent) or any investigational drug within 21 days of cycle 1 day 1. Patients
             receiving radiation therapy within 14 days from cycle 1 day 1. Anti-PD1 or anti-PDL1
             therapy in patients with less than a CR after 18 weeks of such therapy is permitted to
             continue on schedule

          -  Discontinuation from prior anti-PD1 or anti-PDL1 therapy due to immune-related adverse
             event or any other treatment-related adverse event

          -  Autologous transplantation within 100 days

          -  Prior allogeneic transplant within 12 months of initiation on study

          -  Active graft versus host disease (GVHD) within 90 days prior to cycle 1 day 1

          -  Evidence of active central nervous system lymphoma

          -  Pregnant or nursing women

          -  Evidence of chronic active hepatitis B or chronic active hepatitis C infection
             (hepatitis C virus [HCV]), active cytomegalovirus (CMV), or known history of human
             immunodeficiency virus (HIV). If hepatitis B core (HBc) antibody, HCV antibody or CMV
             immunoglobulin (Ig)M is positive, the patient should be correspondingly evaluated for
             the presence of HBV, HCV or CMV by deoxyribonucleic acid (DNA) (polymerase chain
             reaction [PCR]) to determine presence or absence of active infection. If HBc antibody
             is positive, the subject must be evaluated for the presence of hepatitis B virus (HBV)
             DNA by polymerase chain reaction (PCR). If HCV antibody is positive, the subject must
             be evaluated for the presence of HCV ribonucleic acid (RNA) by PCR. Subjects with
             positive HBc antibody and negative HBV DNA by PCR are eligible. Subjects with positive
             HCV antibody and negative HCV RNA by PCR are eligible. Subjects who are
             cytomegalovirus (CMV) IgG or CMV IgM positive but who are CMV DNA negative by PCR are
             eligible

          -  Prior exposure to idelalisib (CAL-101), duvelisib (IPI-145), or any drug that
             specifically inhibits phosphoinositide-3-kinase (PI3K)

          -  Evidence of ongoing active systemic bacterial, fungal or viral infection

          -  Any severe and/or uncontrolled medical conditions or other conditions that could
             affect their participation in the study such as:

               -  Symptomatic, or history of documented congestive heart failure (New York [NY]
                  Heart Association functional classification III-IV)

               -  Significant cardiovascular disease such as uncontrolled or symptomatic
                  arrhythmias, congestive heart failure, or myocardial infarction within 6 months
                  of randomization

               -  Concomitant use of medication known to cause QT prolongation or torsades de
                  pointes. Poorly controlled or clinically significant atherosclerotic vascular
                  disease including cerebrovascular accident (CVA), transient ischemic attack
                  (TIA), angioplasty, cardiac/vascular stenting within 3 months of randomization

          -  Patients with other prior malignancies except for adequately treated basal cell
             carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or
             other cancer from which the patient has been disease-free for 5 years or greater,
             unless approved by the protocol principal investigator

          -  Patients with an active autoimmune disorder (with the exception of autoimmune
             hemolytic anemia, idiopathic thrombocytopenic purpura [ITP] or vitiligo)

          -  History of non-infectious pneumonitis related to prior line of therapy