A Study of SKLB1028 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory (R/R) AML With FLT3-Mutated

NCT04716114 | Unknown Phase 3 DMC

• 1 other identifier: HA114-CSP-003
• Study Type: interventional
• Target: 315
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized，multicenter, open-label Phase III, clinical study to confirm the efficacy and safety of SKLB1028 in patients with relapsed or refractory(R/R) FLT3-Mutated Acute Myeloid Leukemia（AML）compared to salvage chemotherapy.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

monotherapy; SKLB1028

Outcome Measures

Primary Outcomes (2)

• Interim analysis: CR/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 divided by the number of subjects in the response analysis set (RAS).

  up to 4 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 4 years.

Secondary Outcomes (9)

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

  up to 4 years.

• Duration of remission (DOR).

  up to 4 years.

• Duration of Leukemia-Free Survival (LFS)

  up to 4 years.

• Composite complete remission rate

  up to 4 years.

• Time to CR(TTR)

  up to 4 years.

Study Arms (2)

SKLB1028

EXPERIMENTAL

Subjects will receive 150 mg orally twice daily (BID) in continuous 28-day cycles

Drug: SKLB1028

Salvage Chemotherapy

ACTIVE COMPARATOR

Chemotherapy will be given in 28-day cycles. Subjects on low-dose cytarabine (LoDAC) will receive 10 to 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injections for 7 to 14 days. Subjects on azacitidine will receive 75 mg/m\^2 daily by SC or IV, for 5 to 7 days. Subjects on homoharringtonine (HHT), cytarabine and aclarubicin (HAA) will receive 2 mg/m\^2 of HHT by IV, for 7 days (day 1 to 7) (or HHT 2 mg/m\^2, twice daily, day 1 to 3); 100\~200 mg/m\^2 of cytarabine by IV for 7 days (day 1\~7) and 20 mg/d of aclarubicin by IV for 7 days (day 1 to 7). Subjects 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), 1000\~2000 mg/m2 of cytarabine daily by IV for 5 days (day 2 to 6), and 300 g/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 ANC\>0.5 x 10\^9 / L.

Drug: Salvage Chemotherapy

Interventions

SKLB1028 DRUG

SKLB1028 will be administered by oral capsules, 150 mg twice daily (BID).

SKLB1028

Salvage Chemotherapy DRUG

Low-dose cytarabine (LoDAC); azacytidine; homoharringtonine (HHT), cytarabine and aclarubicin (HAA) or fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG) will be administered by subcutaneous (SC) and/or intravenous (IV) injections.

Also known as: cytarabine, azacytidine, fludarabine, homoharringtonine, aclarubicin

Salvage Chemotherapy

Eligibility Criteria

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

You may qualify if:

• Patients volunteered to participate in this study and signed the informed consent form.
• Age≥18 years old, no gender limitation.
• Patient has a diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) as determined by pathological and morphological results, according to World Health Organization (WHO) 2016 classification.
• Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).
• Refractory to first-line AML treatment is defined as: the patient did not achieve complete remission/complete remission with incomplete hematologic recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp) under initial therapy. A patient eligible for standard therapy must receive at least 1 cycle of an anthracycline containing induction therapy in the standard dose for the selected induction regimen. A patient 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 patient as per investigator's assessment.
• Early relapse after first-line AML therapy is defined as: the patients achieved CR/CRi/CRp after first-line treatment, and relapsed within 6 months with hematological relapse.
• Advanced relapse after first-line AML therapy is defined as: the patients achieved CR/CRi/CRp after first-line treatment and relapsed after 6 months with hematological relapse;
• Patient is positive for FLT3 mutation in bone marrow or whole blood.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Patient is eligible for pre-selected salvage chemotherapy according to investigator assessment.
• Patient must meet the following criteria as indicated on the clinical laboratory tests:
• Serum aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x upper limit of normal (ULN);
• Serum total bilirubin ≤ 1.5 x ULN;
• Serum creatinine ≤ 3.0 x ULN or an estimated glomerular filtration rate of \> 30 mL/min.
• Patient is suitable for oral administration of the study drug.

You may not qualify if:

• Patient was diagnosed as acute promyelocytic leukemia (APL), or BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
• Patient has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
• AML with central nervous system (CNS) involvement (defined as highly suspected CNS involvement with clinical symptoms supported by imaging evidence).
• Refractory hypokalemia or hypomagnesemia that is difficult to be corrected by symptomatic treatment and has recurred in the past.
• Patient is currently suffering from clinically significant graft-versus-host disease (GVHD) or receiving systemic cortisol hormone therapy for GVHD.
• Patient has been previously diagnosed with another malignancy (except in the following cases: disease-free for at least 5 years; Patients with treated nonmelanoma skin cancer, breast in situ carcinoma or cervical intraepithelial neoplasia \[regardless of disease status\]; Localized prostate cancer with no recurrence or progression that is expected to be cured after treatment, such as radiotherapy or surgery)
• Patient has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC), hemophilia A, hemophilia B, and von Willebrand disease.
• Patient has had major surgery within 4 weeks prior to the study (the definition of major surgery was based on the level 3 and level 4 surgeries stipulated in the Management Measures for Clinical Application of Medical Technology), or has not fully recovered from any previous invasive operation.
• Patient has radiation therapy within 4 weeks before the first study dose.
• Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 1 month before study entry results in a left ventricular ejection fraction that is ≥ 45%.
• Patient has bradycardia and heart rate is less than 50 beats/min, except for pacemaker user.
• Patients with mean value of triplicate Fridericia-corrected QT interval (QTcF) in the screening period, male \> 450 ms, female \> 470 ms.
• Patients with diagnosed or suspected long QT syndrome at screening (including a family history of long QT syndrome).
• Patients with second degree (Mobitz II) or third degree atrioventricular block disease (except for patients who use the pacemaker).
• Patients with uncontrolled angina or myocardial infarction in 6 months before screening.

Sponsors & Collaborators

• CSPC ZhongQi Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

West China hospital of Sichuan University

Chengdu, Sichuan, China

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

SKLB1028; Cytarabine; Azacitidine; fludarabine; Homoharringtonine; Aclarubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Aza Compounds; Organic Chemicals; Ribonucleosides; Harringtonines; Alkaloids; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Ting Liu, Chief doctor

CONTACT

+862885422364; liuting@scu.edu.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: December 31, 2020
• First Posted: January 20, 2021
• Study Start: March 24, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 2, 2021

Record last verified: 2021-11

Locations

CN (1)