Acute Myelogenous LeukemiaPhase 1NCT04806659
A Phase 1 Study of SH1573 Capsules in Subjects With Refractory or Relapsed Acute Myelogenous Leukemia
A Phase 1 study testing SH1573 Capsules in people with Acute Myelogenous Leukemia, run by Nanjing Sanhome Pharmaceutical, Co., Ltd. at 2 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- SH1573 Capsules
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 2 sitesChina
- Study dates
- 4 Aug 2020to 31 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- 1.Subjects aged ≥18 years.
- 2.Refractory or relapsed AML, or Untreated AML with age ≥70 years if not candidates for standard therapy.
- 3.Subjects must have documented IDH2 mutaion by central testing.
- 4.ECOG performance score of 0 to 2.
- 5.Platelet count ≥ 20,000/μL (transfusions allowed) unless due to underlying malignancy.
- 6.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.
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- 7.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.
- 8.Never participate in other clinical trial in 1 month.
- 9.Patients must sign and date written informed consent prior to admission to the study.
Who cannot join
- 1.Acute promyelocytic leukemia (APL).
- 2.Secondary AML followed by chronic myeloid leukemia (CML).
- 3.Subjects who previously received IDH2 mutation inhibitor.
- 4. 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)
- 5.Subjects who received an non-cytotoxic targeted drug <14 days or 5 half-lives prior to their first day of study drug administration.
- 6.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).
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- 7.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.)
- 8.Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia.
- 9.Subjects with uncontrolled severe infection that required anti-infective therapy.
- 10.Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.
- 11.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.
- Subjects taking medications that are known to prolong the QT interval unless discontinue at least 5 half-lives before the first dose of study drug.
- 12. History of any other malignant tumor unless disease free survival ≥ 1 year (except clinically cured cervical carcinoma in situ, basal cells or squamous epithelial skin cancer).
- 13.Active infection with HIV, syphilis, hepatitis B or C.
- 14.Subjects with known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
- 15.Subjects with uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure > 100 mmHg) .
- 16.Subjects taking the sensitive cytochrome P450 (CYP) substrate medications that have a narrow therapeutic range are excluded from the study unless they can be transferred to other medications within ≥5 half-lives prior to dosing: paclitaxel (CYP2C8) warfarin, phenytoin (CYP2C9), S-mephenytoin (CYP2C19); Subjects taking breast cancer resistant protein (BCRP) transporter, OATP1B1 or OATP1B3 sensitive substrates should be excluded from the study unless they can be transferred to other medications within ≥ 5 half-lives prior to dosing.
- 17.Any disease or conditionins would compromise the safety of the patient or interfere with study assessments in the opinion of the Investigator.
- 18.female with breastfeeding.
- 19.History of hypersensitivity to any active or inactive ingredient of SH1573.
- 20.Subjects with any other conditions deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study participate in the study.
Trial locations and contacts
2 sites in 1 country.
China2 sites, 2 recruiting
- Recruiting
Fujian Medical University Union Hospital
Fuzhou, Fujian, 350001
Jianda Hu, PhD, 86-13959169016, drjiandahu@163.com
- Recruiting
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
Junmin Li, PhD, drlijunmin@126.com
About this study
Official title: A Phase 1, Multicenter, Safety, Pharmacokinetic, and Clinical Activity Study of SH1573 Capsules in Subjects With Refractory or Relapsed Acute Myelogenous Leukemia With an IDH2 Mutation
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.
Read the detailed description
SH1573 is an IDH2 mutation inhibitor.
This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of SH1573 capsules in treatment of subjects with advanced relapsed, refractory acute myeloid leukemias (AML) that harbor an IDH2 mutation.
The study consists of 2 parts: a dose-escalation part (Phase Ia) and a dose-expansion part (Phase Ib). The dose-escalation part will determine the MTD/R2PD. The dose-expansion part will administer the MTD/RP2D to subjects with mIDH2-positive AML.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- SH1573 Capsules
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SH1573 CapsulesDrug
Patients from each cohort will be administered SH1573 capsules every day of 28-day treatment cycles until disease progression or unacceptable toxicities.
| Study group | Role | What they receive |
|---|---|---|
| SH1573 Capsules | Experimental | SH1573 capsules administered orally. Multiple doses will be administered by effiacy and safety to determine the RP2D. Receives: Drug: SH1573 Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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).
Measured: 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)
ORR is defined as the percentage of participants achieving an overall response of CR, CRi, CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML.
Measured: From the first dose of study drug to the time of progressive disease, assessed up to 36 months.
Complete Response (CR) Rate
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).
Measured: From the first dose of study drug to the time of progressive disease, assessed up to 36 months
Duration of Response(DOR)
DOR was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
Measured: From the first dose of study drug to the time of progressive disease, assessed up to 36 months
Overall Survival
Overall survival was defined as the time from the date of first dose until death from any cause and was used to further assess the efficacy of SH1573.
Measured: From the first dose of study drug to the end of study or death, assessed up to 36 months
Time to response (TTR)
TTR is defined as the time from the date of first dose to the date of the first occurrence of response of CR, CRi, CRp, PR, or MLFS based on the 2003 revised IWG criteria for AML.
Measured: From the first dose of study drug to the first response, assessed up to 36 months
Proportion of non-blood transfusion dependent subjects
It is defined as the proportion of subjects who do not need blood transfusion for any sequential period ≥8 weeks during the study treatment period.
Measured: From the first dose of study drug to last dose of study drug, assessed up to 36 months
Maximum serum drug concentration
Blood samples will be obtained from all patients for determination of the maximum serum concentration of SH1573.
Measured: 0, 1, 2, 4, 8, 12, 24, 48, 72 hours post-dose on single dose; 0 hour of cycle1 day 15; 0, 1, 2, 4, 8, 12, 24 hours post-dose on cycle 2 day 1; 0 hour of cycle 2 day 15 and cycle 3 day 1. Each cycle is 28 days.
Area under the concentration-time curve (AUC)
Blood samples will be obtained from all patients for determination of AUC of SH1573.
Measured: 0, 1, 2, 4, 8, 12, 24, 48, 72 hours post-dose on single dose; 0 hour of cycle1 day 15; 0, 1, 2, 4, 8, 12, 24 hours post-dose on cycle 2 day 1; 0 hour of cycle 2 day 15 and cycle 3 day 1. Each cycle is 28 days.
α-Hydroxyglutaric acid (2-HG)
Plasma 2-HG was measured using qualified LC-MS/MS in order to characterize the pharmacodynamic (PD) effects of SH1573.
Measured: 0, 24, 48 hours post-dose on single dose; Day1, Day15 pre-dose on cycle 1 and cycle 2; Day 1 pre-dose on cycle 3 and every 2 cycles afterwards. Each cycle is 28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start4 Aug 2020
- Primary completion31 Aug 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanjing Sanhome Pharmaceutical, Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Junmin Li, PhD, Principal investigator, No.197 Ruijin Er Road, Shanghai, P.R China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04806659
- Sponsor's protocol ID
- SHC016-I-01
- Status last verified
- Mar 2021
- First submitted
- 16 Mar 2021
- Last updated
- 19 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Safety, Pharmacokinetic, and Clinical Activity Study of SH1573 Capsules in Subjects With Refractory or Relapsed Acute Myelogenous Leukemia With an IDH2 Mutation
- ClinicalTrials.gov ID
- NCT04806659
- Acronym / sponsor ID
- SHC016-I-01
- Conditions
- Acute Myelogenous Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Nanjing Sanhome Pharmaceutical, Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 4 Aug 2020 (actual)
- Primary completion
- 31 Aug 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 19 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
SH1573 is an IDH2 mutation inhibitor.
This is a phase 1, open-label, multicenter, single-arm study to evaluate safety, tolerability, PK, PD, and preliminary efficacy of SH1573 capsules in treatment of subjects with advanced relapsed, refractory acute myeloid leukemias (AML) that harbor an IDH2 mutation.
The study consists of 2 parts: a dose-escalation part (Phase Ia) and a dose-expansion part (Phase Ib). The dose-escalation part will determine the MTD/R2PD. The dose-expansion part will administer the MTD/RP2D to subjects with mIDH2-positive AML.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SH1573 Capsules | Experimental | Drug: SH1573 CapsulesSH1573 capsules administered orally. Multiple doses will be administered by effiacy and safety to determine the RP2D. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 1.Subjects aged ≥18 years.
- 2.Refractory or relapsed AML, or Untreated AML with age ≥70 years if not candidates for standard therapy.
- 3.Subjects must have documented IDH2 mutaion by central testing.
- 4.ECOG performance score of 0 to 2.
- 5.Platelet count ≥ 20,000/μL (transfusions allowed) unless due to underlying malignancy.
Key exclusion criteria (25 listed)
- 1.Acute promyelocytic leukemia (APL).
- 2.Secondary AML followed by chronic myeloid leukemia (CML).
- 3.Subjects who previously received IDH2 mutation inhibitor.
- 4. 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)
- 5.Subjects who received an non-cytotoxic targeted drug <14 days or 5 half-lives prior to their first day of study drug administration.
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 |
|---|---|---|
| SH1573 CapsulesPatients from each cohort will be administered SH1573 capsules every day of 28-day treatment cycles until disease progression or unacceptable toxicities. | Drug | SH1573 Capsules |
Primary outcome
Dose-limiting toxicity (DLT)
Time frame: Up to 28 days after first dose of study drug
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.
Number of Participants With Adverse Events (AEs)
Time frame: From the first dose of the study drug to 30 days after the last dose of study drug
The intensity of each AE was graded from 1 to 5 according to the NCI CTCAE Version 5.0.
Rate of CR/CRh (complete remission with incomplete hematologic recovery)
Time frame: From the first dose of study drug to the time of progressive disease, assessed up to 36 months
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).
9 secondary outcomes
Overall Response Rate (ORR)
Time frame: From the first dose of study drug to the time of progressive disease, assessed up to 36 months.
Complete Response (CR) Rate
Time frame: From the first dose of study drug to the time of progressive disease, assessed up to 36 months
Duration of Response(DOR)
Time frame: From the first dose of study drug to the time of progressive disease, assessed up to 36 months
Overall Survival
Time frame: From the first dose of study drug to the end of study or death, assessed up to 36 months
Time to response (TTR)
Time frame: From the first dose of study drug to the first response, assessed up to 36 months
Proportion of non-blood transfusion dependent subjects
Time frame: From the first dose of study drug to last dose of study drug, assessed up to 36 months
Maximum serum drug concentration
Time frame: 0, 1, 2, 4, 8, 12, 24, 48, 72 hours post-dose on single dose; 0 hour of cycle1 day 15; 0, 1, 2, 4, 8, 12, 24 hours post-dose on cycle 2 day 1; 0 hour of cycle 2 day 15 and cycle 3 day 1. Each cycle is 28 days.
Area under the concentration-time curve (AUC)
Time frame: 0, 1, 2, 4, 8, 12, 24, 48, 72 hours post-dose on single dose; 0 hour of cycle1 day 15; 0, 1, 2, 4, 8, 12, 24 hours post-dose on cycle 2 day 1; 0 hour of cycle 2 day 15 and cycle 3 day 1. Each cycle is 28 days.
α-Hydroxyglutaric acid (2-HG)
Time frame: 0, 24, 48 hours post-dose on single dose; Day1, Day15 pre-dose on cycle 1 and cycle 2; Day 1 pre-dose on cycle 3 and every 2 cycles afterwards. Each cycle is 28 days.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2021.
- 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.
Junmin Li, PhD principal investigator
No.197 Ruijin Er Road, Shanghai, P.R China
2 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 SH1573 Capsules in people with Acute Myelogenous Leukemia, run by Nanjing Sanhome Pharmaceutical, Co., Ltd. at 2 sites in China.
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 9 inclusion and 25 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: status not confirmed, as of the sponsor's last update on 19 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Junmin Li, PhD (086-13817712211, drlijunmin@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) (time frame: Up to 28 days after first dose of study drug). The study lists 3 primary outcomes in all. 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 19 Mar 2021.