TriangleNCT03010358 · STUDY IN CONTEXT
Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma
Draft scope assessment: narrower. Linked by condition-string match at the cancer-entity level. The study's eligibility - stage, biomarker, treatment line and prior therapy - has not been reconciled against this page's definition, so its population is narrower than this page in ways not yet recorded. The condition was transformed or resolved through the terminology hierarchy to reach this cancer type, so the link itself is a candidate a reviewer must confirm. Found by searching ClinicalTrials.gov for this cancer type, restricted to studies that have posted results to the registry. No FDA notice, FDA label or NCI summary held by this site cites this study. Because the search asked for posted results, studies without posted results were never looked for, so their absence from this page means nothing.
Read the full study record and all posted results →
Linked outcomes
Will be summarized using descriptive statistics.
The dose of obinutuzumab remains fixed in standard doses while the dose of entospletinib will be escalated. The starting dose of entospletinib will be 200 mg (twice-daily) and escalated to the second dose level 400 mg (twice-daily). MTD is the dose associated with a total of 6 patients treated with less than 2 dose limiting toxicities (DLT), or a total of 3 patients treated with less than 1 DLT. DLT is defined as 1) grade 3 or higher non-hematological toxicity (except grade 3 nausea, vomiting or diarrhea that was reversible within 72 hours with supportive care; grade 3 infusion-related toxicity; asymptomatic grade 3-4 laboratory abnormalities that are reversible to grade 2 or less within 72 hours; grade 3 tumor lysis syndrome or hyponatremia); 2) grade 4 neutropenia lasting \>7 days or febrile neutropenia; or 3) grade 4 thrombocytopenia/anemia or grade 3 thrombocytopenia with bleeding. The dosage follows the 3+3 traditional escalation rules.
Response for CLL/SLL measured using Modified International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 (IWCLL) guidelines. Response for hairy cell leukemia was measured using Consensus resolution: proposed criteria published in Leukemia 1987.
Defined as percentage of participants with complete remission, complete response with incomplete marrow recovery, partial remission and nodular partial response. Response for CLL/SLL measured using Modified International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 (IWCLL) guidelines. Response for hairy cell leukemia was measured using Consensus resolution: proposed criteria published in Leukemia 1987.
Will be summarized descriptively using the Kaplan-Meier estimate. EFS will be censored if entospletinib is discontinued for other reasons (such as drug is no longer available).
Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Will be summarized for the safety population separately for phase 1 and phase 2 portions by dose level. All adverse events (AEs) will be coded by system organ class, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, and severity grade using NCI CTCAE (version 4.03).
Reported safety
Quality of life and patient-reported measures
No linked quality-of-life measure is recorded for this setting and study.
Full draft applicability and source-link record
- trial
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- trial label
- Entospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma
- applicability
- narrower
- applicability note
- Linked by condition-string match at the cancer-entity level. The study's eligibility - stage, biomarker, treatment line and prior therapy - has not been reconciled against this page's definition, so its population is narrower than this page in ways not yet recorded. The condition was transformed or resolved through the terminology hierarchy to reach this cancer type, so the link itself is a candidate a reviewer must confirm.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- provenance class
- registry-condition-search
- discovery note
- Found by searching ClinicalTrials.gov for this cancer type, restricted to studies that have posted results to the registry. No FDA notice, FDA label or NCI summary held by this site cites this study. Because the search asked for posted results, studies without posted results were never looked for, so their absence from this page means nothing.
- outcome Count
- 6
- harms Count
- 2
- qol Count
- 0
- outcomes
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0005
- source section id
- NCT03010358-om-0005
- source outcome index
- 5
- endpoint
- Peripheral Blood B-cell Depletion and Recovery
- endpoint definition
- Will be summarized using descriptive statistics.
- time origin
- Up to 45 months
- analysis role
- exploratory
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- Data for this outcome was not collected due to PI transition.
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0000
- source section id
- NCT03010358-om-0000
- source outcome index
- 0
- endpoint
- Maximum Tolerated Dose (MTD) of Entospletinib in Combination With Obinutuzumab
- endpoint definition
- The dose of obinutuzumab remains fixed in standard doses while the dose of entospletinib will be escalated. The starting dose of entospletinib will be 200 mg (twice-daily) and escalated to the second dose level 400 mg (twice-daily). MTD is the dose associated with a total of 6 patients treated with less than 2 dose limiting toxicities (DLT), or a total of 3 patients treated with less than 1 DLT. DLT is defined as 1) grade 3 or higher non-hematological toxicity (except grade 3 nausea, vomiting or diarrhea that was reversible within 72 hours with supportive care; grade 3 infusion-related toxicity; asymptomatic grade 3-4 laboratory abnormalities that are reversible to grade 2 or less within 72 hours; grade 3 tumor lysis syndrome or hyponatremia); 2) grade 4 neutropenia lasting \>7 days or febrile neutropenia; or 3) grade 4 thrombocytopenia/anemia or grade 3 thrombocytopenia with bleeding. The dosage follows the 3+3 traditional escalation rules.
- time origin
- Up to 28 days
- analysis role
- primary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- Source null
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0001
- source section id
- NCT03010358-om-0001
- source outcome index
- 1
- endpoint
- Complete Response (CR) Defined as the Percentage of Subjects Who Achieve CR
- endpoint definition
- Response for CLL/SLL measured using Modified International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 (IWCLL) guidelines. Response for hairy cell leukemia was measured using Consensus resolution: proposed criteria published in Leukemia 1987.
- time origin
- Up to 45 months
- analysis role
- primary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- Efficacy evaluable population: participants with CLL (Phase I/Phase II)
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0002
- source section id
- NCT03010358-om-0002
- source outcome index
- 2
- endpoint
- Objective Response Rate (ORR)
- endpoint definition
- Defined as percentage of participants with complete remission, complete response with incomplete marrow recovery, partial remission and nodular partial response. Response for CLL/SLL measured using Modified International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 (IWCLL) guidelines. Response for hairy cell leukemia was measured using Consensus resolution: proposed criteria published in Leukemia 1987.
- time origin
- Up to 45 months
- analysis role
- secondary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- Efficacy evaluable population: participants with CLL (Phase I/Phase II)
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0003
- source section id
- NCT03010358-om-0003
- source outcome index
- 3
- endpoint
- Event Free Survival (EFS)
- endpoint definition
- Will be summarized descriptively using the Kaplan-Meier estimate. EFS will be censored if entospletinib is discontinued for other reasons (such as drug is no longer available).
- time origin
- The interval between the date of first study treatment and the date of objective signs of disease recurrence, subsequent anti leukemic therapy, or death, whichever is first reported, assessed up to 45 months.
- analysis role
- secondary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- Efficacy evaluable population: participants with CLL (Phase I/Phase II)
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0004
- source section id
- NCT03010358-om-0004
- source outcome index
- 4
- endpoint
- Number of Participants Who Experienced Adverse Events
- endpoint definition
- Will be assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Will be summarized for the safety population separately for phase 1 and phase 2 portions by dose level. All adverse events (AEs) will be coded by system organ class, Medical Dictionary for Regulatory Activities (MedDRA) preferred term, and severity grade using NCI CTCAE (version 4.03).
- time origin
- Up to 45 months
- analysis role
- secondary
- reporting status
- POSTED
- data cutoff
- Source null
- population note
- Source null
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- arms
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0000
- arm key
- OG000
- arm label
- Phase 1, Dose 1-2
- regimen
- 2 groups of patients in phase 1 study. Phase 1, Dose 1 received entospletinib at Dose Level 1: 400 mg daily (200 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 1, Dose 2 received entospletinib at Dose Level 2: 800 mg daily (400 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study.
- analyzed count
- 9
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT03010358-om-0000#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0001
- arm key
- OG000
- arm label
- All Research Participants
- regimen
- The Outcome Measure was assessed in aggregate, combining participants from both phases of the study, as per the planned protocol. Phase 1, Dose 1 received entospletinib at Dose Level 1: 400 mg daily (200 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 1, Dose 2 received entospletinib at Dose Level 2: 800 mg daily (400 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 2, MTD: Received entospletinib at Maximum Tolerated Dose (MTD) in combination with obinutuzumab during Dose Expansion phase of study. The MTD was determined to be 800 mg daily (400 mg twice daily).
- analyzed count
- 21
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT03010358-om-0001#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0002
- arm key
- OG000
- arm label
- All Research Participants
- regimen
- The Outcome Measure was assessed in aggregate, combining participants from both phases of the study, as per the planned protocol. Phase 1, Dose 1 received entospletinib at Dose Level 1: 400 mg daily (200 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 1, Dose 2 received entospletinib at Dose Level 2: 800 mg daily (400 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 2, MTD: Received entospletinib at Maximum Tolerated Dose (MTD) in combination with obinutuzumab during Dose Expansion phase of study. The MTD was determined to be 800 mg daily (400 mg twice daily).
- analyzed count
- 21
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT03010358-om-0002#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0003
- arm key
- OG000
- arm label
- All Research Participants
- regimen
- The Outcome Measure was assessed in aggregate, combining participants from both phases of the study, as per the planned protocol. Phase 1, Dose 1 received entospletinib at Dose Level 1: 400 mg daily (200 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 1, Dose 2 received entospletinib at Dose Level 2: 800 mg daily (400 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 2, MTD: Received entospletinib at Maximum Tolerated Dose (MTD) in combination with obinutuzumab during Dose Expansion phase of study. The MTD was determined to be 800 mg daily (400 mg twice daily).
- analyzed count
- 21
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT03010358-om-0003#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0004
- arm key
- OG000
- arm label
- Phase 1, Dose 1 (400 mg Entospletinib Daily)
- regimen
- Patients receive entospletinib PO either QD or BID on days -7 to -1 (run-in phase) according to dose level 1 (200 mg twice daily). Patients also receive obinutuzumab IV on days 1, 2, 8, and 15 of the first cycle, and on day 1 of subsequent cycles. Treatment with obinutuzumab repeats every 28 days for up to 6 cycles and daily treatment with entospletinib continues every 28 days for up to 12 cycles in the absence of disease progression or unexpected toxicity. Entospletinib: Given PO Laboratory Biomarker Analysis: Correlative studies Obinutuzumab: Given IV Pharmacological Study: Correlative studies
- analyzed count
- 6
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT03010358-om-0004#groups/OG000
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0004
- arm key
- OG001
- arm label
- Phase 2 and MTD (800 mg Entospletinib Daily)
- regimen
- Patients receive entospletinib PO either QD or BID on days -7 to -1 (run-in phase) according to dose level 2 (400 mg twice daily). Patients also receive obinutuzumab IV on days 1, 2, 8 and 15 of the first cycle, and on day 1 of subsequent cycles. Treatment with obinutuzumab repeats every 28 days for up to 6 cycles and daily treatment with entospletinib continues every 28 days for up to 12 cycles in the absence of disease progression or unexpected toxicity. Entospletinib is administered PO.
- analyzed count
- 17
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT03010358-om-0004#groups/OG001
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- outcome key
- om-0005
- arm key
- OG000
- arm label
- All Research Participants
- regimen
- The Outcome Measure was assessed in aggregate, combining participants from both phases of the study, as per the planned protocol. Phase 1, Dose 1 received entospletinib at Dose Level 1: 400 mg daily (200 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 1, Dose 2 received entospletinib at Dose Level 2: 800 mg daily (400 mg twice daily) in combination with obinutuzumab during Dose Escalation phase of study. Phase 2, MTD: Received entospletinib at Maximum Tolerated Dose (MTD) in combination with obinutuzumab during Dose Expansion phase of study. The MTD was determined to be 800 mg daily (400 mg twice daily).
- analyzed count
- 0
- analyzed unit
- Participants
- is comparator
- Source null
- source pointer
- NCT03010358-om-0005#groups/OG000
- harms
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- harm key
- EG000
- source section id
- NCT03010358-ae
- event group key
- EG000
- event group label
- Phase 1, Dose 1 (400 mg Entospletinib Daily)
- serious affected
- 3
- serious at risk
- 6
- other affected
- 6
- other at risk
- 6
- frequency threshold
- 5
- collection period
- Up to 45 months. For the participants, the median follow-up time for adverse events was 17 months.
- event definition
- Per protocol; "Safety data will be summarized for the safety population separately for phase 1 and phase 2 portions by dose level. All AEs will be coded by system organ class, MedDRA preferred term, and severity grade using NCI CTCAE (v 4.03)." Since Phase 2 and the subset of Phase I patients who received MTD both received 800 mg daily, these are reported together. Those who received 400 mg daily were reported separately.
- undenominated note
- Source null
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- release id
- clinical-indications-draft-1
- disease state id
- ds-prolymphocytic-leukemia
- nct id
- NCT03010358
- harm key
- EG001
- source section id
- NCT03010358-ae
- event group key
- EG001
- event group label
- Phase 2 and MTD (800 mg Entospletinib Daily)
- serious affected
- 5
- serious at risk
- 17
- other affected
- 17
- other at risk
- 17
- frequency threshold
- 5
- collection period
- Up to 45 months. For the participants, the median follow-up time for adverse events was 17 months.
- event definition
- Per protocol; "Safety data will be summarized for the safety population separately for phase 1 and phase 2 portions by dose level. All AEs will be coded by system organ class, MedDRA preferred term, and severity grade using NCI CTCAE (v 4.03)." Since Phase 2 and the subset of Phase I patients who received MTD both received 800 mg daily, these are reported together. Those who received 400 mg daily were reported separately.
- undenominated note
- Source null
- curation status
- draft
- reviewed by
- Source null
- reviewed at
- Source null
- created at
- 2026-09-10T00:00:00Z
- quality of life
- setting source links
Preserved source evidence · Not medical advice