Non-Hodgkin LymphomaPhase 1/2NCT02568683
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 1/2 study testing Entospletinib and Vincristine in people with Non-Hodgkin Lymphoma, run by Gilead Sciences at 7 sites in 2 countries.
Trial summary
The primary objective of this study is to evaluate the safety of ENTO with VCR in participants with relapsed or refractory B-cell NHL. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma
- What is being tested?
- Entospletinib and Vincristine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 11 Feb 2016to 22 Jun 2017
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
France5 sites
Centre Hospitalier Universitaire de Dijon Hôpital du Bocage
Dijon
Centre Hospitalier Régional Universitaire de Lille (CHRU de Lille)
Lille, Hauts-de-France
Institut Paoli Calmettes
Marseille, Provence-Alpes-Côte d'Azur Region
Groupe Hospitalier du Haut Leveque
Pessac, Aquitaine
Centre Hospital Lyon Sud
Pierre-Bénite
United States2 sites
Medical University of South Carolina
Charleston, South Carolina
Forrest General Hospital
Hattiesburg, Mississippi
About this study
Official title: 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)
The primary objective of this study is to evaluate the safety of ENTO with VCR in participants with relapsed or refractory B-cell NHL.
- Conditions
- Non-Hodgkin Lymphoma
- Being tested
- Entospletinib, Vincristine
- Keywords
- DLBCL, Relapsed, Refractory
- Medical subject headings
- Lymphoma, Non-Hodgkin, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntospletinibDrug
Also called GS-9973, ENTO
ENTO spray dried dispersion tablets administered orally twice daily while in a fasted state
VincristineDrug
Also called VCR
VCR administered intravenously
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation: ENTO | Experimental | 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. Receives: Drug: Entospletinib; Drug: Vincristine |
| Dose Expansion: VCR+ENTO (Cohort A) | Experimental | 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. Receives: Drug: Entospletinib; Drug: Vincristine |
| Dose Expansion: VCR+ENTO (Cohort B) | Experimental | 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. Receives: Drug: Entospletinib; Drug: Vincristine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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)
Measured: Cycle 1 (28-day cycle)
Secondary outcomes (3)
Number of Participants With AEs and Lab Abnormalities Not Defined as DLTs in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage
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.
Measured: Cycle 1 (28-day cycle)
Duration of Exposure to ENTO
Measured: Baseline to end of study (maximum: 24 weeks)
Number of VCR Doses
Measured: Baseline to end of study (maximum: 24 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2015 (estimated)
- Study start11 Feb 2016
- Primary completion3 Oct 2016
- Study completion22 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02568683
- Sponsor's protocol ID
- GS-US-339-1562
- Other IDs
- 2015-002731-17, 2015
- Status last verified
- Mar 2019
- First submitted
- 30 Sep 2015
- Last updated
- 17 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02568683
- Acronym / sponsor ID
- GS-US-339-1562
- Conditions
- Non-Hodgkin Lymphoma
- Keywords
- DLBCL, Relapsed, Refractory
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 11 Feb 2016 (actual)
- Primary completion
- 3 Oct 2016 (actual)
- Study completion
- 22 Jun 2017 (actual)
- First posted
- 6 Oct 2015 (estimated)
- Results
- Posted 17 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety of ENTO with VCR in participants with relapsed or refractory B-cell NHL.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: ENTO | Experimental | Drug: Entospletinib, Drug: VincristineParticipants 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. |
| Dose Expansion: VCR+ENTO (Cohort A) | Experimental | Drug: Entospletinib, Drug: VincristineBased 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. |
| Dose Expansion: VCR+ENTO (Cohort B) | Experimental | Drug: Entospletinib, Drug: VincristineBased 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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:
- 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.
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EntospletinibAlso: GS-9973, ENTOENTO spray dried dispersion tablets administered orally twice daily while in a fasted state | Drug | Dose Escalation: ENTO, Dose Expansion: VCR+ENTO (Cohort A), Dose Expansion: VCR+ENTO (Cohort B) |
| VincristineAlso: VCRVCR administered intravenously | Drug | Dose Escalation: ENTO, Dose Expansion: VCR+ENTO (Cohort A), Dose Expansion: VCR+ENTO (Cohort B) |
Primary outcome
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
Time frame: Cycle 1 (28-day cycle)
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)
3 secondary outcomes
Number of Participants With AEs and Lab Abnormalities Not Defined as DLTs in Participants With Relapsed or Refractory B-cell NHL: Dose Escalation Stage
Time frame: Cycle 1 (28-day cycle)
Duration of Exposure to ENTO
Time frame: Baseline to end of study (maximum: 24 weeks)
Number of VCR Doses
Time frame: Baseline to end of study (maximum: 24 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gilead Study Director study director
Gilead Sciences
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Entospletinib and Vincristine in people with Non-Hodgkin Lymphoma, run by Gilead Sciences at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Cycle 1 (28-day cycle)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2019.