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This is a single-arm, open, multicenter, phase 2 study to evaluate the efficacy, safety and pharmacokinetics of HYLM-122 in combination with cytarabine in Chinese subjects with FLT3 positive relapsed or refractory acute myeloid leukemia.
This study will have two phases. Phase 1: the escalation phase is to establish the recommended phase 2 dose (RP2D) of HYML-122 given in combination with cytarabine.
Phase 2: the extension phase study will treat patients with FLT3 positive relapsed or refractory AML with HYML-122 in combination with cytarabine at the RP2D, and further evaluate efficacy and safety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HYML-122 plus cytarabine | Experimental | The first three eligible enrolled patients will be treated with initial dosing of HYML-122 400mg bid daily and cytarabine 100mg/m2 intravenously by using "3+3" escalating design to explore RP2D. the Data Monitoring Committee (DMC) will evaluate the safety, efficacy and PK data of the phase 1 subjects and establish the combined regimen recommended dose. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgement of the investigator, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet 1 of the discontinuation criteria, whichever occurs first. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HYML-122; cytarabine | Drug | HYML-122 is administered orally consecutive with 400mg bid or 600mg bid or dose adjusted by DMC judgement in each 28-day treatment cycle. cytarabine is administered by intravenous infusion with 100mg/m2 or dose adjusted by DMC judgement once daily on the first to 7th day of each treatment cycle. Upon completion of each 28-day treatment cycle, patients may continue to receive HYML-122 and cytarabine if they are benefit from the treatment and the toxicity is tolerable. |
| Measure | Description | Time Frame |
|---|---|---|
| ORR | overall remission rate, including complete remission without minimum residual disease (CRMRD-), complete remission (CR), complete remission with incomplete hematologic recovery (CRi), complete remission without platelet recovery (CRp), partial remission (PR). | up to 24 months |
| composite complete remission (CRc) rate | CRc rate is defined as the rate of all complete and incomplete remission (CRMRD-+CR+CRp+CRi). | up to 24 months. |
| Measure | Description | Time Frame |
|---|---|---|
| RFS | relapse-free survival, for patients achieving a complete remission, defined as the interval from the date of first documentation of a leukemia free state to date of recurrence, treatment failure, death due to any cause or last contact of the end-of-study follow up, which ever occurs first. | up to 24 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yang Shu, MD. BS. | Contact | +8613918983465 | shuyang@tarapeutics.com |
| Name | Affiliation | Role |
|---|---|---|
| Depei Wu, MD. PhD | The First Affiliated Hospital of Soochow University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| the First Affiliated Hospital of Soochow University | Recruiting | Suzhou | Jiangsu | 215006 | China |
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| ID | Term |
|---|---|
| D012008 | Recurrence |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007951 | Leukemia, Myeloid |
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| ID | Term |
|---|---|
| D003561 | Cytarabine |
| ID | Term |
|---|---|
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
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level 1: HYML-122 400mg bid (day1-day28) in combination with Cytarabine 100mg/m2 (day1-day7). each cycle is 28 days.
level2: HYML-122 600mg bid (day1-day28) in combination with Cytarabine 100mg/m2 (day1-day7). each cycle is 28 days.
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|
| EFS |
event-free survival, EFS is defined as the time from the date of enrollment until the date of documented relapse from CR, CRp or CRi, treatment failure, death from any cause or last contact of the end-of-study follow-up, whichever occurs first. |
| up to 24 months |
| OS | overall survival, OS is defined as time from the date of enrollment until the date of death from any cause. For a subject who is not known to have died buy the end-of-study follow-up, OS is censored at the date of last contact. | up to 24 months |
| DOR-CR | duration of CR remission, DOR-CR is defined as the time from the date of first CR, CRp, CRi until the date of documented relapse. | up to 24 months |
| Incidence of treatment-emergent adverse events (TEAEs) | safety and tolerability of investigational product assessed as the number of participants experience adverse events (AEs, CTCAE 5.0) or abnormalities in vital signs, laboratory tests, or electrocardiograms. | up to 24 months |
| Cmax,ss | Peak plasma concentration at steady state (Cmax,ss) | at the end of Cycle 1 (each cycle is 28 days) |
| Cmin,ss | minimum observed plasma concentration at steady state (Cmin,ss) of drug in blood plasma | at the end of Cycle 1 (each cycle is 28 days) |
| Cav,ss | the average steady-state plasma concentration | at the end of Cycle 1 (each cycle is 28 days) |
| AUCss | the area under the plasma concentration at steady-state | at the end of Cycle 1 (each cycle is 28 days) |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006571 |
| Heterocyclic Compounds |
| D001087 | Arabinonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |