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Phase 1 Study of SGI-110 in Patients With Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
SGI-110
Sponsored by
Otsuka Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female patients with a diagnosis of AML (WHO classification 2008).

    • Patients, 20 years of age or older, who are unresponsive to standard chemotherapy or have relapsed following standard chemotherapy
    • Patients, 65 years of age or older, who are not eligible for standard intensive chemotherapy
  • Patients with ECOG performance status (PS) of 0 to 2
  • Patients with adequate organ function
  • Women of child-bearing potential must not be pregnant or breast feeding (pregnancy test will be performed at Screening). Women of child bearing potential and all men with female partners of child bearing potential must practice two medically acceptable methods of birth control and must not become pregnant or father a child while receiving treatment with SGI-110 and for 3 months following last dosing.
  • Patients who have undergone prior allogeneic hematopoietic stem cell transplantation must have no evidence of active graft-versus host disease (GVHD) and must be off immunosuppressive therapy by ≥2 weeks prior to IMP administration.

Exclusion Criteria:

  • Patients with acute promyelocytic leukemia accompanied by t(15;17)(q22;q12) or (PML/RARA) karyotype abnormalities (include other variant types of APL)
  • Patients with multiple cancers (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 3 years)
  • Subjects with life-threatening illnesses other than AML or MDS, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at risk.
  • Patients with poorly controlled arrhythmias, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
  • Patients with symptomatic central nervous system involvement.

Sites / Locations

  • kinki Region
  • Kanto
  • Kyusyu

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort1

Cohort2

Cohort3

Cohort4

Arm Description

SGI-110 36mg/m2 will be administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28).

SGI-110 60mg/m2 will be administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28).

SGI-110 90mg/m2 will be administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28).

SGI-110 60mg/m2 will be administered subcutaneously once daily for 10 days (Day 1 to Day 5 and Day 8 to Day 12 with dosing, Day 6 and 7 with non-dosing), followed by a 16-day non-dosing period (Day 13 to Day 28).

Outcomes

Primary Outcome Measures

Dose Limiting Toxicity (DLT)
DLT was defined as any of the following adverse events (AEs) occurring during Course 1 for which there was a reasonable probability or possibility of a causal relationship with the IMP. The severity of AEs was graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Nonhematologic toxicity of Grade ≥3, except for (i) nausea, vomiting, or diarrhea of Grade 3 that is controllable by optimal therapy, and (ii) Grade 3 laboratory findings other than serum creatinine, bilirubin, aspartate aminotransferase, or alanine aminotransferase. Grade 4 thrombocytopenia that was not present at trial entry and that is not resolved within 7 days Grade 4 neutropenia that was not present at trial entry and that is not resolved within 7 days Febrile neutropenia (defined as a neutrophil count of <500/μL accompanied by a fever of ≥38°C) Any AE that results in a delay of >4 weeks in starting the next treatment course

Secondary Outcome Measures

Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110

Full Information

First Posted
November 14, 2014
Last Updated
February 12, 2021
Sponsor
Otsuka Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02293993
Brief Title
Phase 1 Study of SGI-110 in Patients With Acute Myeloid Leukemia
Official Title
Phase 1 Study of SGI-110 in Patients With Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
January 7, 2015 (Actual)
Primary Completion Date
June 14, 2017 (Actual)
Study Completion Date
May 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Co., Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
To evaluate the tolerability and pharmacokinetics of SGI-110 when administered subcutaneously to Japanese patients with acute myeloid leukemia (AML).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort1
Arm Type
Experimental
Arm Description
SGI-110 36mg/m2 will be administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28).
Arm Title
Cohort2
Arm Type
Experimental
Arm Description
SGI-110 60mg/m2 will be administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28).
Arm Title
Cohort3
Arm Type
Experimental
Arm Description
SGI-110 90mg/m2 will be administered subcutaneously once daily for 5 consecutive days (Day 1 to Day 5), followed by a 23-day non-dosing period (Day 6 to Day 28).
Arm Title
Cohort4
Arm Type
Experimental
Arm Description
SGI-110 60mg/m2 will be administered subcutaneously once daily for 10 days (Day 1 to Day 5 and Day 8 to Day 12 with dosing, Day 6 and 7 with non-dosing), followed by a 16-day non-dosing period (Day 13 to Day 28).
Intervention Type
Drug
Intervention Name(s)
SGI-110
Primary Outcome Measure Information:
Title
Dose Limiting Toxicity (DLT)
Description
DLT was defined as any of the following adverse events (AEs) occurring during Course 1 for which there was a reasonable probability or possibility of a causal relationship with the IMP. The severity of AEs was graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Nonhematologic toxicity of Grade ≥3, except for (i) nausea, vomiting, or diarrhea of Grade 3 that is controllable by optimal therapy, and (ii) Grade 3 laboratory findings other than serum creatinine, bilirubin, aspartate aminotransferase, or alanine aminotransferase. Grade 4 thrombocytopenia that was not present at trial entry and that is not resolved within 7 days Grade 4 neutropenia that was not present at trial entry and that is not resolved within 7 days Febrile neutropenia (defined as a neutrophil count of <500/μL accompanied by a fever of ≥38°C) Any AE that results in a delay of >4 weeks in starting the next treatment course
Time Frame
28 days (Day 1 to Day 29)
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time Frame
Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12)
Title
Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time Frame
Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12)
Title
Area Under the Plasma Concentration-time Curve From Time Zero to 24 Hours (AUC24h) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time Frame
Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12)
Title
Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110
Time Frame
Pre-dose, 15min, 30min, 60min, 90min, 2h, 3h, 4h, 6h, 8h, 24h after dosing (Cohorts 1, 2, and 4: Day 1 and Day 5, Cohort 3: Day 1 and Day 12)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female patients with a diagnosis of AML (WHO classification 2008). Patients, 20 years of age or older, who are unresponsive to standard chemotherapy or have relapsed following standard chemotherapy Patients, 65 years of age or older, who are not eligible for standard intensive chemotherapy Patients with ECOG performance status (PS) of 0 to 2 Patients with adequate organ function Women of child-bearing potential must not be pregnant or breast feeding (pregnancy test will be performed at Screening). Women of child bearing potential and all men with female partners of child bearing potential must practice two medically acceptable methods of birth control and must not become pregnant or father a child while receiving treatment with SGI-110 and for 3 months following last dosing. Patients who have undergone prior allogeneic hematopoietic stem cell transplantation must have no evidence of active graft-versus host disease (GVHD) and must be off immunosuppressive therapy by ≥2 weeks prior to IMP administration. Exclusion Criteria: Patients with acute promyelocytic leukemia accompanied by t(15;17)(q22;q12) or (PML/RARA) karyotype abnormalities (include other variant types of APL) Patients with multiple cancers (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 3 years) Subjects with life-threatening illnesses other than AML or MDS, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, or put the study outcomes at risk. Patients with poorly controlled arrhythmias, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification Patients with symptomatic central nervous system involvement.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Junji Ikeda
Organizational Affiliation
Otsuka Pharmaceutical Co., Ltd.
Official's Role
Study Director
Facility Information:
Facility Name
kinki Region
City
Kyoto
Country
Japan
Facility Name
Kanto
City
Region
Country
Japan
Facility Name
Kyusyu
City
Region
Country
Japan

12. IPD Sharing Statement

Learn more about this trial

Phase 1 Study of SGI-110 in Patients With Acute Myeloid Leukemia

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