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

NCT02293993 | Completed Phase 1 Results

• 2 other identifiers: 343-14-001JapicCTI-142711
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 3

Brief Summary

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

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• 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

  28 days (Day 1 to Day 29)

Secondary Outcomes (4)

• Maximum Plasma Concentration (Cmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110

  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)

• Time to Maximum Plasma Concentration (Tmax) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110

  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)

• 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

  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)

• Terminal-phase Elimination Half-life (T1/2,z) of SGI-110 and Its Active Metabolite Decitabine Following Single and Multiple Administration of SGI-110

  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)

Study Arms (4)

Cohort1

EXPERIMENTAL

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).

Drug: SGI-110

Cohort2

EXPERIMENTAL

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).

Drug: SGI-110

Cohort3

EXPERIMENTAL

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).

Drug: SGI-110

Cohort4

EXPERIMENTAL

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).

Drug: SGI-110

Interventions

SGI-110 DRUG

Cohort1; Cohort2; Cohort3; Cohort4

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Otsuka Pharmaceutical Co., Ltd.: lead

Study Sites (3)

kinki Region

Kyoto, Japan

Location

Kanto

Region, Japan

Location

Kyusyu

Region, Japan

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

guadecitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: Otsuka Pharmaceutical Co., LTD.

CL_OPCJ_RDA_Team@otsuka.jp

+81-3-6361-7366

Study Officials

• Junji Ikeda

  Otsuka Pharmaceutical Co., Ltd.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 14, 2014
• First Posted: November 19, 2014
• Study Start: January 7, 2015
• Primary Completion: June 14, 2017
• Study Completion: May 31, 2019
• Last Updated: March 5, 2021
• Results First Posted: March 5, 2021

Record last verified: 2021-02

Locations

JP (3)