A Study of XY0206 Versus Salvage Chemotherapy In Patients With Relapsed or Refractory AML With FLT3-ITD-Mutation (ALIVE)

NCT05876832 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: XY0206AML3001
• Study Type: interventional
• Target: 312
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine the clinical benefit of XY0206 therapy in participants with FLT3-ITD mutated AML who are refractory to or have relapsed after prior AML therapy as shown with overall survival (OS) compared to salvage chemotherapy. In addition, this study is also to investigate the efficacy of XY0206 as assessed by CR/CRh rate in these subjects。

Conditions

Acute Myeloid Leukemia With FLT3/ITD Mutation

Outcome Measures

Primary Outcomes (2)

• Interim analysis: Complete remission(CR)/CR with partial hematologic recovery(CRh) rate in the experimental group.

  The complete remission and complete remission with partial hematological recovery (CR/CRh) rate was defined as the number of subjects who achieved either CR or CRh at any of the postbaseline visits divided by the number of subjects in the analysis population.

  up to 3 years.

• The final analysis: Overall Survival(OS).

  Overall survival was defined as the time from the date of randomization until the date of death from any cause.

  up to 3 years .

Secondary Outcomes (10)

• Key secondary end point: Event-Free Survival (EFS).

  up to 3 years.

• Key secondary end point: CR/CRh rate .

  up to 3 years.

• CR rate.

  up to 3 years.

• Duration of remission (DOR).

  up to 3 years.

• Composite complete remission rate.

  up to 3 years.

Study Arms (2)

XY0206

EXPERIMENTAL

XY0206 will be administered orally once a day in continuous 28-day cycles.

Drug: XY0206

Salvage chemotherapy

ACTIVE COMPARATOR

Participants will receive salvage chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) injection for 10 days. Participants on azacitidine will receive 75 mg/m\^2 daily by SC or IV injection for 7 days.Participants on fludarabine, cytarabine and granulocyte colony-stimulating factor (G-CSF) (FLAG) will receive 30 mg/m\^2 of fludarabine daily by IV for 5 days (day 2 to 6), 1\~2 g/m2 of cytarabine daily by IV for 5 days (day 2 to 6), and 300 μg/m\^2 of G-CSF daily by SC or IV for 5 days (days 1 to 5). After completion of chemotherapy, G-CSF will be administered continually until absolute neutrophil count(ANC)\>0.5 x 10\^9 / L. Participants on mitoxantrone, etoposide, cytarabine(MEC) will receive 8 mg/m\^2 of mitoxantrone daily by IV for 3 days (day 1 to 3), 100 mg/m2 of etoposide daily by IV for 7 days (day 1 to 7), and 100 mg/m\^2 of cytarabine daily by IV for 7 days (days 1 to 7)

Drug: Salvage Chemotherapy

Interventions

XY0206 DRUG

Dosage form:Tablet;Multiple dose phase:Take the medicine once a day,37.5mg at a time.4 weeks of continuous medication is one course of treatment. After the first course of treatment, the subjects can continue to receive the experimental drug treatment until the subjects meet the withdrawal criteria.

XY0206

Salvage Chemotherapy DRUG

Low-dose Cytarabine (LoDAC) or azacitidine, fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) or mitoxantrone, etoposide, cytarabine (MEC)will be administered by subcutaneous (SC) and/or intravenous (IV) injections.

Salvage chemotherapy

Eligibility Criteria

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

You may qualify if:

• Age≥18 years old.
• Subject has a diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) according to World Health Organization (WHO) classification as determined by pathology review at the treating institution.
• Subject is refractory to or relapsed after prior AML therapy (with or without hematopoietic stem cell transplant ):
• Advanced relapse after first-line AML therapy is defined as: the patients achieved Complete remission without minor residual diseases/complete remission/complete remission with partial hematologic recovery/complete remission with incomplete hematologic recovery/complete remission with incomplete platelet recovery/Morphologic leukemia- free state(CRMRD-/CR/CRh/CRi/CRp/MLFS )after first-line treatment and relapsed after 12 months with hematological relapse;
• Patients with relapsed / refractory AML.
• Refractory to first-line AML therapy is defined as:the patient did not achieve CRMRD-/CR/CRh/CRi/CRp/MLFS under initial therapy.A subject eligible for standard therapy must receive at least 1 cycle of an anthracycline containing induction block in standard dose for the selected induction regimen. A subject not eligible for standard therapy must have received at least 1 complete block of induction therapy seen as the optimum choice of therapy to induce remission for this subject.
• Early relapse:Relapse within 12 months after consolidation therapy after achieving CRMRD-/CR/CRh/CRi/CRp/MLFS.
• Relapse after 12 months but nonresponse to conventional chemotherapy after achieving CRMRD-/CR/CRh/CRi/CRp/MLFS.
• Second or more relapse.
• Patients who cannot tolerate intensive chemotherapy develop disease progression during continuous treatment with low-intensity drugs.
• Persistence of extramedullary leukemia.
• Patient is positive for FLT3-ITD mutation in bone marrow or whole blood.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Expected survival ≥12 weeks .
• Patient must meet the following criteria as indicated on the clinical laboratory tests:

You may not qualify if:

• Patient was diagnosed as acute promyelocytic leukemia (APL), or Philadelphia chromosome（BCR-ABL）-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Patients who received live vaccine (including live attenuated vaccine) within 4 weeks before randomization and/or planed to receive live vaccine after enrollment.
• Presence of FLT3-tyrosine kinase domain(TKD) mutation.
• Patients were prior failed adequate treatment with FLT3 inhibitors.
• AML with Central Nervous System Leukemia.
• Patient has AML secondary to prior chemotherapy for other neoplasms, except for MDS.
• Patients with other malignant tumors past or present,unless whose Disease-free survival period≥5 years.Non-melanin skin cancer, carcinoma in situ, or cervical intraepithelial neoplastic lesions with completed radical treatment (regardless of disease-free survival),and subjects with prostate cancer confined to the prostate and with no evidence of disease recurrence or progression,if they have started hormonal therapy or have undergone surgery to remove the malignancy or have undergone radical radiotherapy,will be eligible for the study.
• Pretrial treatment conditions:
• Patients who received hematopoietic stem cell transplantation within the 2 months before enrollment,or having clinically significant graft-versus-host disease (GVHD) or receiving systemic cortisol hormone therapy for GVHD.
• Patients who received chemotherapy, biological therapy, targeted anti-tumor therapy within 14 days before the first use of the drug in this study or within 5 half-lives of the drug, or radiation therapy within 28 days.
• Patients who participated in other clinical trials and received trial drugs within 28 days to the first study dose.
• Patients who have had major surgery or significant traumatic injury within 28 days to the first study dose or planted to require major surgery during study treatment.
• Concurrent disease conditions:
• Patients are hepatitis B surface antigen or core antibody actives positive,and hepatitis B virus(HBV) DNA ≥2000IU/mL or 1×104 copy/mL.
• Patients are hepatitis C virus (HCV) antibody actives positive and HCV-RNA quantification is above the upper limit of normal at each center.

Sponsors & Collaborators

• Shijiazhuang Yiling Pharmaceutical Co. Ltd: lead

Central Study Contacts

Wang wei, master

CONTACT

086-0311-66703017; wangwei001@yiling.cn

Jianxiang Wang, MD

CONTACT

022-23909120; wangjx@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2023
• First Posted: May 25, 2023
• Study Start: June 15, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: May 26, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share