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Entospletinib (ENTO) as Monotherapy and in Combination With Chemotherapy in Japanese Adults (Japanese AML)

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ClinicalTrials.gov Identifier: NCT03135028
Recruitment Status : Terminated (No signal of efficacy with Entospletinib)
First Posted : May 1, 2017
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief 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

Condition or disease Intervention/treatment Phase
Hematologic Malignancy Acute Myeloid Leukemia Drug: Entospletinib Drug: Daunorubicin Drug: Cytarabine Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 9 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : May 18, 2017
Actual Primary Completion Date : December 15, 2017
Actual Study Completion Date : February 26, 2019


Arm Intervention/treatment
Experimental: Entospletinib Monotherapy
Participants with relapsed or refractory hematologic malignancies will receive entospletinib twice daily (BID) of every 28 day cycle until participants meet treatment discontinuation criteria or do not experience clinical benefit
Drug: Entospletinib
400 mg tablet (s) orally twice daily
Other Name: GS-9973

Experimental: Entospletinib + cytarabine + daunorubicin

Lead-in (Cycle 0): Participants with previously untreated AML will receive entospletinib BID for 14 days

Induction (Up to 2 cycles): Entospletinib 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 will have the option to receive post-remission therapy with entospletinib BID in combination with high-dose cytarabine (Hi-DAC) for up to four 28 day cycles

Drug: Entospletinib
400 mg tablet (s) orally twice daily
Other Name: GS-9973

Drug: Daunorubicin
60 mg/m^2 administered intravenously daily on Days 1 to 3 of each 28-day induction cycle

Drug: Cytarabine

100 mg/m^2 intravenous (IV) administration twice daily on Days 1 to 7 of each 28-day induction cycle

3g/m^2 IV administration twice daily on days 1, 3 and 5 (<=60 years of age) or 1g/m^2 IV administration once daily on days 1-5 (>60 years of age) of each 28-day post-remission cycle (Hi-DAC)





Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) and Laboratory Abnormalities Defined as dose limiting toxicities (DLT) [ Time Frame: Up to Cycle 1 Day 28 with expansion to 8 weeks after Cycle 1 Day 1 in the arm of combination treatment ]

Secondary Outcome Measures :
  1. Incidence of Adverse Events (AEs) and Laboratory Abnormalities Not Defined as dose limiting toxicities (DLT) [ Time Frame: Up to 30 days after permanent discontinuation of study treatment ]
  2. Pharmacokinetic (PK) Parameter: AUCtau of entospletinib [ Time Frame: Predose and 2 hours Postdose ]
    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  3. Pharmacokinetic (PK) Parameter: Cmax of entospletinib [ Time Frame: Predose and 2 hours Postdose ]
    Cmax is defined as the maximum observed concentration of drug.

  4. Pharmacokinetic (PK) Parameter: Tmax of entospletinib [ Time Frame: Predose and 2 hours Postdose ]
    Tmax is defined as the time (observed time point) of Cmax

  5. Pharmacokinetic (PK) Parameter: t1/2 of entospletinib [ Time Frame: Predose and 2 hours Postdose ]
    t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

  6. Pharmacokinetic (PK) Parameter: Ctau of entospletinib [ Time Frame: Predose and 2 hours Postdose ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Group A ENTO monotherapy: relapsed or refractory hematologic malignancies by World Health Organisation (WHO) criteria and who are not eligible to receive standard of care
  • Group B ENTO + cytarabine + daunorubicin: 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:

  • Known active central nervous system or leptomeningeal leukemic involvement
  • Ongoing liver injury, known chronic active hepatitis C Virus (HCV), chronic active hepatitis B Virus (HBV)

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03135028


Locations
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Japan
University of Fukui Hospital
Fukui, Japan, 910-1193
Kyushu University Hospital
Fukuoka, Japan, 812-8582
Tokai University Hospital
Kanagawa, Japan, 259-1193
Tohoku University Hospital
Miyagi, Japan, 980-8574
NTT Medical Center Tokyo
Tokyo, Japan, 141-8625
Kindai University Hospital
Ōsaka, Japan, 589-8511
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Director: Gilead Study Director Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT03135028     History of Changes
Other Study ID Numbers: GS-US-429-4104
First Posted: May 1, 2017    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Cytarabine
Daunorubicin
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors