Hematologic MalignancyPhase 1Japanese AMLNCT03135028
Entospletinib (ENTO) as Monotherapy and in Combination With Chemotherapy in Japanese Adults
A Phase 1 study testing Entospletinib, Daunorubicin and Cytarabine in people with Hematologic Malignancy and Acute Myeloid Leukemia, run by Gilead Sciences at 6 sites in Japan.
Trial summary
The primary objective of this study is to evaluate the safety and tolerability of entospletinib (ENTO) monotherapy and in combination with chemotherapy in Japanese participants. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancy, Acute Myeloid Leukemia
- What is being tested?
- Entospletinib, Daunorubicin and Cytarabine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 6 sitesJapan
- Study dates
- 19 May 2017to 26 Feb 2019
- Phase
- Phase 1
- 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
- ENTO monotherapy (Group A): relapsed or refractory hematologic malignancies by World Health Organisation (WHO) criteria and who are not eligible to receive standard of care
- ENTO + cytarabine + daunorubicin (Group B): previously untreated AML by WHO criteria, who are deemed fit for cytarabine and daunorubicin (7+3) induction chemotherapy and are able to undergo up to 2 cycles of induction chemotherapy, as determined by the treating physician
- Must have been born in Japan and must not have lived outside of Japan for a period > 1 year in the 5 years prior to Day 1 of study treatment
- Must be able to confirm the Japanese origin of their maternal and paternal ancestry
Who cannot join
- Known active central nervous system or leptomeningeal leukemic involvement
- Ongoing liver injury, or known infection with chronic active hepatitis C virus (HCV) or chronic active hepatitis B virus (HBV)
- NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Japan6 sites
University of Fukui Hospital
Fukui, 910-1193
Kyushu University Hospital
Fukuoka, 812-8582
Tokai University Hospital
Kanagawa, 259-1193
Tohoku University Hospital
Miyagi, 980-8574
Kindai University Hospital
Ōsaka, 589-8511
NTT Medical Center Tokyo
Tokyo, 141-8625
About this study
Official title: A Phase 1b Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Entospletinib (ENTO) as Monotherapy in Japanese Subjects With Relapsed or Refractory Hematologic Malignancies and in Combination With Chemotherapy in Japanese Subjects With Previously Untreated Acute Myeloid Leukemia (AML)
The primary objective of this study is to evaluate the safety and tolerability of entospletinib (ENTO) monotherapy and in combination with chemotherapy in Japanese participants.
- Conditions
- Hematologic Malignancy, Acute Myeloid Leukemia
- Being tested
- Entospletinib, Daunorubicin, Cytarabine
- Keywords
- Relapsed or Refractory Hematologic Malignancy, Previously untreated AML
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myeloid, Acute, 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
400 mg (2 × 200 mg tablets) orally twice daily
DaunorubicinDrug
60 mg/m^2 administered intravenously daily on Days 1 to 3 of each 28-day induction cycle
CytarabineDrug
100 mg/m^2 intravenous administration twice daily on Days 1 to 7 of each 28-day induction cycle
Hi-DAC: 3 g/m^2 IV administration twice daily on days 1, 3, and 5 (≤ 60 years of age) or 1 g/m^2 IV administration once daily on Days 1 to 5 (> 60 years of age) of each 28-day post-remission cycle
| Study group | Role | What they receive |
|---|---|---|
| ENTO monotherapy (Group A) | Experimental | Participants with relapsed or refractory hematologic malignancies will receive ENTO twice daily of every 28-day cycle until participants meet treatment discontinuation criteria or do not experience clinical benefit. Receives: Drug: Entospletinib |
| ENTO + cytarabine + daunorubicin (Group B) | Experimental | Lead-in (Cycle 0): Participants with previously untreated AML will receive ENTO twice daily for 14 days.
Induction (Up to 2 cycles): ENTO in combination with daunorubicin and cytarabine for up to two 28-day cycles.
Post-remission chemotherapy (at least 2 cycles, up to 4 cycles): Some participants (who have achieved complete remission [CR] or morphologic complete remission with incomplete blood count recovery [CRi] and do not require or cannot proceed to allogeneic stem cell transplantation [SCT] and participants who are awaiting a donor or transitioning to allogeneic SCT per investigator discretion) will have the option to receive post-remission chemotherapy with ENTO twice daily in combination with high-dose cytarabine (Hi-DAC) for up to four 28-day cycles. Receives: Drug: Entospletinib; Drug: Daunorubicin; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT)
Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT:
- Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue.
- In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC > 500/μL) or platelet count (>25000/μL) within 28 days
- Grade 4, clinically significant, electrolyte abnormalities that were not correctable within 24 hours
- Liver function test abnormalities that did not resolve to Grade 2 within 10 days
- Infection that resulted from unexpectedly complicated prolonged myelosuppression
- Toxicities that required temporary interruption of treatment and did not resolve to Grade 2 within 10 days or ENTO was suspended or dose reduced for a period of more than 10 days.
Measured: Cycle 1 (28-day cycle)
Secondary outcomes (2)
Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT
Measured: Day 1 Up to 30 days after permanent discontinuation of study treatment (maximum approximately 80 weeks)
Plasma Concentration of ENTO
Plasma concentration of drug (ENTO) over different time points is reported.
Measured: Cycle 1 (28-days cycle) Day 8 at 0 (predose), 1, 2, 3, 4, 6, 8, and 12 hours postdose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2017
- Study start19 May 2017
- Primary completion26 Feb 2019
- Study completion26 Feb 2019
Why it stopped: No signal of efficacy with Entospletinib
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 Hematologic MalignancyStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 9 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
- NCT03135028
- Sponsor's protocol ID
- GS-US-429-4104
- Acronym
- Japanese AML
- Status last verified
- Feb 2020
- First submitted
- 26 Apr 2017
- Last updated
- 6 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b Study to Investigate the Safety, Tolerability, and Pharmacokinetics of Entospletinib (ENTO) as Monotherapy in Japanese Subjects With Relapsed or Refractory Hematologic Malignancies and in Combination With Chemotherapy in Japanese Subjects With Previously Untreated Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT03135028
- Acronym / sponsor ID
- Japanese AML / GS-US-429-4104
- Conditions
- Hematologic Malignancy, Acute Myeloid Leukemia
- Keywords
- Relapsed or Refractory Hematologic Malignancy, Previously untreated AML
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No signal of efficacy with Entospletinib
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 19 May 2017 (actual)
- Primary completion
- 26 Feb 2019 (actual)
- Study completion
- 26 Feb 2019 (actual)
- First posted
- 1 May 2017 (actual)
- Results
- Posted 6 Mar 2020
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 and tolerability of entospletinib (ENTO) monotherapy and in combination with chemotherapy in Japanese participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ENTO monotherapy (Group A) | Experimental | Drug: EntospletinibParticipants with relapsed or refractory hematologic malignancies will receive ENTO twice daily of every 28-day cycle until participants meet treatment discontinuation criteria or do not experience clinical benefit. |
| ENTO + cytarabine + daunorubicin (Group B) | Experimental | Drug: Entospletinib, Drug: Daunorubicin, Drug: CytarabineLead-in (Cycle 0): Participants with previously untreated AML will receive ENTO twice daily for 14 days. Induction (Up to 2 cycles): ENTO in combination with daunorubicin and cytarabine for up to two 28-day cycles. Post-remission chemotherapy (at least 2 cycles, up to 4 cycles): Some participants (who have achieved complete remission [CR] or morphologic complete remission with incomplete blood count recovery [CRi] and do not require or cannot proceed to allogeneic stem cell transplantation [SCT] and participants who are awaiting a donor or transitioning to allogeneic SCT per investigator discretion) will have the option to receive post-remission chemotherapy with ENTO twice daily in combination with high-dose cytarabine (Hi-DAC) for up to four 28-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ENTO monotherapy (Group A): relapsed or refractory hematologic malignancies by World Health Organisation (WHO) criteria and who are not eligible to receive standard of care
- ENTO + cytarabine + daunorubicin (Group B): previously untreated AML by WHO criteria, who are deemed fit for cytarabine and daunorubicin (7+3) induction chemotherapy and are able to undergo up to 2 cycles of induction chemotherapy, as determined by the treating physician
- Must have been born in Japan and must not have lived outside of Japan for a period > 1 year in the 5 years prior to Day 1 of study treatment
- Must be able to confirm the Japanese origin of their maternal and paternal ancestry
Key exclusion criteria (3 listed)
- Known active central nervous system or leptomeningeal leukemic involvement
- Ongoing liver injury, or known infection with chronic active hepatitis C virus (HCV) or chronic active hepatitis B virus (HBV)
- NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
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, ENTO400 mg (2 × 200 mg tablets) orally twice daily | Drug | ENTO + cytarabine + daunorubicin (Group B), ENTO monotherapy (Group A) |
| Daunorubicin60 mg/m^2 administered intravenously daily on Days 1 to 3 of each 28-day induction cycle | Drug | ENTO + cytarabine + daunorubicin (Group B) |
| Cytarabine100 mg/m^2 intravenous administration twice daily on Days 1 to 7 of each 28-day induction cycle Hi-DAC: 3 g/m^2 IV administration twice daily on days 1, 3, and 5 (≤ 60 years of age) or 1 g/m^2 IV administration once daily on Days 1 to 5 (> 60 years of age) of each 28-day post-remission cycle | Drug | ENTO + cytarabine + daunorubicin (Group B) |
Primary outcome
Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT)
Time frame: Cycle 1 (28-day cycle)
Occurrence of any of the following toxicities, attributable to ENTO, during Cycle 1 was considered DLT: * Grade 4 non-hematologic toxicity except alopecia, nausea, and vomiting controllable with anti-emetic therapy, line associated venous thrombosis, infection-related toxicities such as fever/sepsis, and fatigue. * In participants without bone marrow evidence of hematologic malignancy, hematologic toxicity defined as failure to recover absolute neutrophil count (ANC > 500/μL) or platelet count (>25000/μL) within 28 days * Grade 4, clinically significant, electrolyte abnormalities that were not correctable within 24 hours * Liver function test abnormalities that did not resolve to Grade 2 within 10 days * Infection that resulted from unexpectedly complicated prolonged myelosuppression * Toxicities that required temporary interruption of treatment and did not resolve to Grade 2 within 10 days or ENTO was suspended or dose reduced for a period of more than 10 days.
2 secondary outcomes
Percentage of Participants With AEs and Laboratory Abnormalities Not Defined as DLT
Time frame: Day 1 Up to 30 days after permanent discontinuation of study treatment (maximum approximately 80 weeks)
Plasma Concentration of ENTO
Time frame: Cycle 1 (28-days cycle) Day 8 at 0 (predose), 1, 2, 3, 4, 6, 8, and 12 hours postdose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Entospletinib, Daunorubicin and Cytarabine in people with Hematologic Malignancy and Acute Myeloid Leukemia, run by Gilead Sciences at 6 sites in Japan.
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 4 inclusion and 3 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 6 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Japan. 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 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.
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 6 Mar 2020). 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?
Percentage of Participants With Adverse Events (AEs) and Laboratory Abnormalities Defined as Dose Limiting Toxicities (DLT) (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 6 Mar 2020.