A Phase 1 Study of SH1573 Capsules in Subjects With Refractory or Relapsed Acute Myelogenous Leukemia

NCT04806659 | Unknown Phase 1

• 1 other identifier: SHC016-I-01
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 2

Brief Summary

An open label single-arm clinical trial to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of SH1573 in subjects with advanced relapsed, refractory acute myelogenous leukemia that harbor an IDH2 mutation.

Conditions

Acute Myelogenous Leukemia

Outcome Measures

Primary Outcomes (3)

• Dose-limiting toxicity (DLT)

  DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 （28 days every cycle）and is at least possibly related to study drug.

  Up to 28 days after first dose of study drug

• Number of Participants With Adverse Events (AEs)

  The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 5.0.

  From the first dose of the study drug to 30 days after the last dose of study drug

• Rate of CR/CRh (complete remission with incomplete hematologic recovery)

  CR was defined as \< 5% blasts in the bone marrow and full recovery of peripheral blood counts (platelets \> 100 x 10\^9/L and ANC \> 1.0 x 10\^9/L); CRh was defined as \< 5% blasts in the bone marrow and partial recovery ofperipheral blood counts (platelets \> 50 x 10\^9/L and ANC \> 0.5 x 10\^9/L).

  From the first dose of study drug to the time of progressive disease, assessed up to 36 months

Secondary Outcomes (9)

• Overall Response Rate (ORR)

  From the first dose of study drug to the time of progressive disease, assessed up to 36 months.

• Complete Response (CR) Rate

  From the first dose of study drug to the time of progressive disease, assessed up to 36 months

• Duration of Response(DOR)

  From the first dose of study drug to the time of progressive disease, assessed up to 36 months

• Overall Survival

  From the first dose of study drug to the end of study or death, assessed up to 36 months

• Time to response (TTR)

  From the first dose of study drug to the first response, assessed up to 36 months

Study Arms (1)

SH1573 Capsules

EXPERIMENTAL

SH1573 capsules administered orally. Multiple doses will be administered by effiacy and safety to determine the RP2D.

Drug: SH1573 Capsules

Interventions

SH1573 Capsules DRUG

Patients from each cohort will be administered SH1573 capsules every day of 28-day treatment cycles until disease progression or unacceptable toxicities.

SH1573 Capsules

Eligibility Criteria

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

You may qualify if:

• Subjects aged ≥18 years.
• Refractory or relapsed AML, or Untreated AML with age ≥70 years if not candidates for standard therapy.
• Subjects must have documented IDH2 mutaion by central testing.
• ECOG performance score of 0 to 2.
• Platelet count ≥ 20,000/μL (transfusions allowed) unless due to underlying malignancy.
• AST, ALT ≤ 3.0 x ULN unless due to underlying malignancy, and Serum total bilirubin ≤ 1.5 x ULN unless due to Gilbert's disease, a gene mutation in UGT1A1, or leukemic organ involvement; Serum creatinine ≤1.5 x ULN or creatinine clearance \> 40 mL/min based on the Cockroft-Gault formula.
• Female subjects with reproductive potential must have a negative serum pregnancy test within 72 hours prior to the start of therapy. Females of child-bearing potential and male patients should be willing to use barrier contraception during the study and until 6 months after completion of studyusing adequate contraceptive measures throughout the study.
• Never participate in other clinical trial in 1 month.
• Patients must sign and date written informed consent prior to admission to the study.

You may not qualify if:

• Acute promyelocytic leukemia (APL).
• Secondary AML followed by chronic myeloid leukemia (CML).
• Subjects who previously received IDH2 mutation inhibitor.
• \. Subjects who received systemic anticancer therapy or radiotherapy \<14 days prior to their first day of study drug administration. (Hydroxyurea is allowed for the control of peripheral leukemic blasts)
• Subjects who received an non-cytotoxic targeted drug \<14 days or 5 half-lives prior to their first day of study drug administration.
• Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose,or subjects on immunosuppressive therapy post HSCT at the time of screening, or with clinically significant graft-versus-host disease (GVHD).
• Subjects with any clinically relevant toxic effects of any prior treatment of cancer. (Subjects with residual Grade 1 toxicity are allowed with approval of the Medical Monitor.)
• Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia.
• Subjects with uncontrolled severe infection that required anti-infective therapy.
• Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
• Any of the following cardiac criteria:
• Active cardiac disease in 6 month before the first dose, such as New York Heart Association (NYHA) Class III or IV congestive heart failure, acute coronary syndrome or stroke.
• Left ventricular ejection fraction (LVEF) ≤ 40%.
• Mean resting corrected QT interval (QTcF) \> 470(female) or 450(male) msec.
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome.

Sponsors & Collaborators

• Nanjing Sanhome Pharmaceutical, Co., Ltd.: lead

Study Sites (2)

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• Junmin Li, PhD

  No.197 Ruijin Er Road, Shanghai, P.R China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junmin Li, PhD

CONTACT

086-13817712211; drlijunmin@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2021
• First Posted: March 19, 2021
• Study Start: August 4, 2020
• Primary Completion: August 31, 2023
• Study Completion: December 31, 2023
• Last Updated: March 19, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)