A Clinical Study to investigate the Safety and Efficacy of Entospletinib (ENTO) in combination with standard of care in adult subjects with Non-Hodgkin Lymphoma (NHL).

Phase 1

Conditions: Relapsed or refractory B-cell Non-Hodgkin Lymphoma and relapsed or refractory Diffuse Large B-cell Lymphoma.
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-002731-17-HU

Lead Sponsor: Gilead Sciences, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 94

Inclusion Criteria

1) Subjects = 18 years of age
2) Measurable disease by computed tomograph (CT)/ and/or positron- emission tomography CT (PET-CT)
3) A) Dose Escalation Stage: Confirmed Diagnosis of relapsed or refractory Non-Hodgkin Lymphoma (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:
i) 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.
ii) 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
4) Eastern Cooperative Oncology Group (ECOG) performance status = 2 or Karnofsky performance status = 70
5) Adequate organ function defined by the screening laboratory inclusion listed below and Left Ventricular Ejection Fraction (LVEF) = 45% confirmed by ECHO or MUGA

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

1) Diagnosis of Primary Mediastinal Large B-cell Lymphoma
2) A life threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety or interfere with the absorption or metabolism of ENTO
3) Active or symptomatic CNS disease or epidural involvement
4) Uncontrolled intercurrent illness including, but not limited to, unstable angina pectoris or psychiatric illness/social situations that would limit compliance with study requirements
5) 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)
6) Contraindication to receive VCR or any planned protocol-specified chemotherapy
7) Eligible for autologous stem cell transplant
8) History of myelodysplastic syndrome, allogeneic stem cell or solid organ transplantation
9) History of any other non-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