Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Vincristine

Tubulin Modulators

Antimitotic Agents

Participants will be enrolled sequentially in a 3 + 3 dose escalation design to receive escalating dose of ENTO+VCR at dose levels 1 to 4 with the objective of defining the maximum tolerated dose (MTD) or recommended dose for the dose expansion stage. Following the determination of the MTD of the dose levels 1 to 4 (or concurrently with the opening of dose level 4), the safety of administering ENTO with VCR when administered as a 4-day prolonged continuous infusion may be evaluated in the continuous infusion dose escalation level (dose level C1) with the objective of investigating the schedule of dosing ENTO when administered with VCR as a continuous infusion.

Based on the tolerability, safety, and efficacy data from the dose escalation phase, participants with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) may receive VCR+ENTO.

Based on the tolerability, safety, and efficacy data from the dose escalation phase, participants with relapsed or refractory B-cell NHL (non-DLBCL) may receive VCR+ENTO.

ENTO spray dried dispersion tablets administered orally twice daily while in a fasted state

Entospletinib

Gilead Study Director

The primary objective of this study is to evaluate the safety of ENTO with VCR in participants with relapsed or refractory B-cell NHL.

Safety and Efficacy of Entospletinib (ENTO [GS-9973]) Combined With Vincristine (VCR) in Adult Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)

A Phase 1b-2, Open-Label, Dose Escalation and Expansion Study Evaluating the Safety and Efficacy of Entospletinib (ENTO [GS-9973]) Combined With Vincristine (VCR) in Adult Subjects With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)

Occurrence of any of the following toxicities during Cycle 1 was considered DLT if judged by the Investigator to be possibly, probably, or definitely related to the administration of any drug in the treatment regimen:

* Grade 4 (or higher) non-hematologic toxicity
* Grade 3 non-hematologic toxicity lasting ≥ 7 days despite optimal supportive care

  * Note: Grade 3 or higher neuropathy was considered DLT if occurring during Cycle 1 regardless of duration.
* Any Grade 3 non-hematologic laboratory value if:

  * Medical intervention was required to treat the patient, or
  * Abnormality led to hospitalization, or
  * Abnormality persisted for \> 1 week
* Grade 4 Neutropenia (absolute neutrophil count \[ANC\] \< 500 /μL) persisting for \> 14 days or associated with febrile neutropenia
* Grade 4 thrombocytopenia (platelets \< 25,000 cells/μL) persisting for \> 14 days (or \> 25,000 cells/μL, but requiring prophylactic platelet transfusion to maintain this level)

The number of participants with AEs and lab abnormalities not defined as DLTs in participants in the dose escalation stage with relapsed or refractory B-cell NHL are presented.

Gilead Sciences

Full Analysis Set included all participants who received at least 1 dose of ENTO.

Participants received ENTO 200 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.

ENTO 200 mg

Participants received ENTO 400 mg tablet twice daily + VCR 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 8 weeks.

ENTO 400 mg

Total

Age, Continuous

Sex: Female, Male

Race

Race/Ethnicity, Customized

Ethnicity

Because the study was terminated after enrolling only 10 participants, the dose expansion stage and the planned efficacy analyses were not conducted.

Gilead Clinical Study Information Center

DLT Analysis Set included participants in the Full Analysis Set (included all participants who received at least 1 dose of ENTO) who received 37 of 56 Cycle 1 doses of ENTO and completed the full Cycle 1 dose of VCR or who experienced a DLT during the DLT assessment window.

Number of Participants With Adverse Events (AEs) and Laboratory (Lab) Abnormalities Defined as Dose Limiting Toxicities (DLTs) in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage

AEs not defined as DLTs

Lab abnormalities not defined as DLTs

Participants in the Full Analysis Set were analyzed.

Number of Participants With AEs and Lab Abnormalities Not Defined as DLTs in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage

Duration of Exposure to ENTO

Number of VCR Doses

Participants received entospletinib (ENTO) 200 mg tablet twice daily + vincristine (VCR) 1.0 mg/m\^2 administered via intravenous infusion every 14 days; up to 24 weeks.

Spots Global Cancer Trial Database for Safety and Efficacy of Entospletinib (ENTO [GS-9973]) Combined With Vincristine (VCR) in Adult Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial