Clinical trial NCT02568683 (phase 1/phase 2, status: terminated)
Conditions: non-hodgkin lymphoma
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: entospletinib, vincristine
SMILES: C1CN(CCO1)C1=CC=C(C=C1)N=C1NC(=CN2C=CN=C12)C1=CC2=NNC=C2C=C1, CC[C@]1(O)C[C@@H]2CN(C1)CCC1=C(NC3=CC=CC=C13)[C@@](C2)(C(=O)OC)C1=C(OC)C=C2N(C=O)[C@@H]3[C@]4(CCN5CC=C[C@](CC)([C@@H]45)[C@@H](OC(C)=O)[C@]3(O)C(=O)OC)C2=C1
Eligibility criteria:

        Key Inclusion Criteria:

          -  Measurable disease by computed tomograph (CT)/ and/or positron-emission tomography CT
             (PET-CT)

          -  A) Dose Escalation Stage: Confirmed diagnosis of relapsed or refractory B-Cell NHL
             treated with prior treatment for lymphoid malignancy comprising of at least 1 regimen
             containing a therapeutic anti-CD20 antibody (eg, rituximab, ofatumumab, GA-101) and at
             least 2 prior combination chemotherapy regimens (or autologous stem cell transplant) ,
             or treated with 1 prior combination chemotherapy regimen in patients without an
             approved second-line therapy option, requiring treatment in the opinion of the
             treating physician

          -  B) Dose Expansion Cohorts:

               -  Expansion Cohort A: Diagnosis of relapsed or refractory DLBCL treated with prior
                  treatment for lymphoid malignancy comprising of at least 1 regimen containing a
                  therapeutic anti-CD20 antibody (eg, rituximab, ofatumumab, GA-101) and at least 2
                  prior combination chemotherapy regimens or autologous stem cell transplant, or
                  treated with 1 prior combination chemotherapy regimen in patients without an
                  approved second-line therapy option, requiring treatment in the opinion of the
                  treating physician

               -  Expansion Cohort B: Diagnosis of relapsed or refractory B-cell NHL (other than
                  DLBCL) treated with prior treatment for lymphoid malignancy comprising of at
                  least 1 regimen containing a therapeutic anti-CD20 antibody (eg, rituximab,
                  ofatumumab, GA-101) and at least 2 prior combination chemotherapy regimens or
                  autologous stem cell transplant, or treated with 1 prior combination chemotherapy
                  regimen in patients without an approved second-line therapy option, requiring
                  treatment in the opinion of the treating physician

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 or Karnofsky
             performance status ≥ 70

          -  Required screening laboratory data (within 2 weeks prior to administration of study
             drug) as defined in study protocol.

          -  Adequate organ function defined by the screening laboratory inclusion and Left
             Ventricular Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram (ECHO) or
             multigated acquisition (MUGA)

          -  Discontinuation of all therapy (including radiotherapy, chemotherapy, tyrosine kinase
             inhibitors (TKIs), immunotherapy, or investigational therapy for the treatment of
             cancer at least 2 weeks prior to the initiation of study therapy

          -  All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before
             enrollment, with the exception of alopecia (any grade permitted)

          -  For female individuals of childbearing potential, willingness to use a
             protocol-recommended method of contraception from the Screening visit throughout the
             study and 30 days from the last dose of ENTO or VCR, whichever is later.

          -  For male individuals having intercourse with females of childbearing potential,
             willingness to abstain from heterosexual intercourse or use a protocol-recommended
             method of contraception from the start of study drug throughout the study treatment
             period and for 90 days following the last dose of ENTO or VCR, whichever is later and
             to refrain from sperm donation from the start of the study drug throughout the study
             treatment period and for 90 days following the last dose of ENTO or VCR, whichever is
             later.

          -  In the judgment of the investigator, participation in the protocol offers an
             acceptable benefit-to-risk ratio when considering current disease status, medical
             condition, and the potential benefits and risks of alternative treatments for the
             individual's NHL

          -  Willingness to comply with scheduled visits, drug administration plan, imaging
             studies, laboratory tests, other study procedures, and study restrictions

          -  Have the ability to understand and sign a written informed consent form, which must be
             obtained prior to initiation of study procedures

        Key Exclusion Criteria:

          -  Diagnosis of Primary Mediastinal Large B-cell Lymphoma

          -  A life threatening illness, medical condition or organ system dysfunction which, in
             the investigator's opinion, could compromise the individual's safety or interfere with
             the absorption or metabolism of ENTO

          -  Active or symptomatic central nervous system (CNS) disease or epidural involvement

          -  Uncontrolled intercurrent illness including, but not limited to, unstable angina
             pectoris or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Current/ongoing Neuropathy (sensory or motor) Grade > 1 or any history of Grade ≥ 3
             neuropathy with prior VCR or chemotherapy exposure (documentation by history is
             adequate to exclude)

          -  Contraindication to receive VCR or any planned protocol-specified chemotherapy

          -  Eligible for autologous stem cell transplant

          -  History of myelodysplastic syndrome, allogeneic stem cell or solid organ
             transplantation

          -  History of any other prior lymphoid malignancy other than the registrational histology
             or any other non-lymphoid malignancy except for the following: adequately treated
             local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ,
             superficial bladder cancer, asymptomatic prostate cancer without known metastatic
             disease and with no requirement for therapy or requiring only hormonal therapy and
             with normal prostate specific antigen for ≥ 1 year prior to the start of study drug,
             or any other cancer that has been in complete remission without treatment for ≥ 5
             years prior to enrollment

          -  Known hypersensitivity or intolerance to any of the active substances or excipients in
             the formulations for ENTO

          -  Evidence of uncontrolled systemic bacterial, fungal, or viral infection at the start
             of study drug

          -  Ongoing drug-induced liver injury, chronic active Hepatitis C Virus (HCV), chronic
             active Hepatitis B Virus (HBV), human immunodeficiency virus (HIV), alcoholic liver
             disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic
             obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension

          -  Current therapy with proton pump inhibitors

          -  Pregnancy or breastfeeding

          -  Ongoing active pneumonitis

          -  Prior treatment with a spleen tyrosine kinase (SYK) inhibitor

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.