A Study of GLB-001 in Patients With Myeloid Malignancies

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase 1, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of GLB-001 in Patients With Myeloid Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06378437
• Other study ID #: GLB-001-02
• Status: Recruiting
• Phase: Phase 1
• Start date: May 24, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: June 2024
• Source: Hangzhou GluBio Pharmaceutical Co., Ltd.
• Contact: Jing Liu, Ph.D.
• Phone: 86-18616699599
• Email: Jing.Liu[@]glubiotx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study GLB-001-02 is a phase 1, open-label clinical study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of GLB-001 in study participants with relapsed or refractory or intolerant myeloid malignancies including polycythemia vera (PV), essential thrombocythemia (ET), myelofibrosis (MF), lower-risk myelodysplastic syndrome (LR-MDS), higher-risk myelodysplastic syndromes (HR-MDS), and acute myeloid leukemia (AML). This study consists of 3 parts, dose escalation (Phase 1a), dose exploration (Phase 1b) and dose expansion (Phase 1c). Dose escalation (Phase 1a) and dose exploration (Phase 1b) will evaluate the safety, tolerability, PK, PD and preliminary efficacy of GLB-001, administered orally, in study participants with PV/ET, or study participants with MF/LR-MDS/HR-MDS/AML, respectively. Dose expansion (Phase 1c) will be followed to determine the relationships among dose, exposure, toxicity, tolerability and clinical activity, to identify minimally active dose, and to select the recommended dose(s) for phase 2 study. Approximately 108 study participants may be enrolled in the study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Study participants must understand and voluntarily sign a written informed consent form (ICF) prior to any study-related assessments/procedures being performed.

• Study participants is =18 years of age at the time of signing the ICF.

• Study participants with confirmed diagnosis of relapsed or refractory or intolerant myeloid malignancies including PV, ET, primary myelofibrosis (PMF), MDS and AML according to 2022 World Health Organization (WHO) criteria classification, and post-polycythemia vera myelofibrosis (post-PV MF) and post-essential thrombocythemia myelofibrosis (post-ET MF) according to the 2013 IWG-MRT criteria.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0,1 or 2.

• Life expectancy > 3 months.

• Good performance of major organs, including hematology, liver and kidney function, and coagulation. etc.

• Study participants are willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

• Study participants with acute promyelocytic leukemia (APL).

• Receipt of following anticancer medications/therapies prior to the first dose of GLB-001: (1) study participants with PV or ET who received treatment with hydroxyurea within 2 days prior to the first dose, or any other treatment for PV or ET within 7 days prior to first dose of GLB-001, (2) study participants with MF who received any type of treatment for MF within 14 days prior to the first dose, such as chemotherapy, immunotherapy, radiotherapy and erythropoietin, androgens, thrombopoietin or granulocyte colony-stimulating factor, (3) study participants with LR-MDS who received any type of treatment for MDS within 14 days prior to the first dose, (4) study participants with HR-MDS or AML who received chimeric antigen receptor T cell therapy (CAR-T) or other biologic therapy within 28 days prior to the first dose of GLB-001, or received any other anticancer therapies within 14 days prior to the first dose of GLB-001.

• Receipt of any other investigational drug study within 28 days or 5 half-lives of that study drug before the first dose of GLB-001.

• Study participants with unresolved clinically significant non-hematologic toxicities that were = Grade 1 or failed to recover to baseline levels following prior anticancer therapies (with the exception of alopecia or skin hyperpigmentation).

• Study participants who are scheduled to receive other anticancer therapies or other investigational drugs during the study period.

• Study participants with active acute or chronic graft versus host disease (GVHD) requiring systemic immunosuppressive therapy.

• Receipt of autologous stem cell transplantation (ASCT) within the last 3 months prior to the first dose of GLB-001, or allogeneic hematopoietic stem cell transplantation (allo-HSCT) within the last 6 months prior to the first dose of GLB-001.

• Study participants with known active involvement in central nervous system (CNS).

• Study participants with peripheral neuropathy = Grade 2 (Graded according to CTCAE version 5.0).

• Study participants have a history of known malignancy other than the inclusion diagnosis for the past 5 years, with the exception of curatively resected cancer in situ, including cervical carcinoma in situ, basal cell carcinoma of the skin, or prostate cancer in situ, etc.

• QT interval interval > 470 milliseconds (ms) using electrocardiographic (ECG) at screening.

• Study participants have impaired cardiac function or clinically significant cardiac disease at current or within last 6 months.

• Study participants with known active infection of hepatitis B virus (HBV) or hepatitis C virus C (HCV).

• Study participants with known human immunodeficiency virus (HIV) infection.

• Study participants with known life-threatening or clinical significant uncontrolled active systemic infections unrelated to malignant hematologic diseases.

• Study participants with a state condition that may alter affects the absorption, distribution, metabolism and excretion of GLB-001 after judgment of the investigator.

• Medications or supplements that are known to be strong and moderate inhibitors or inducers of cytochrome P-450 isozyme 3A (CYP3A) and/or P-glycoprotein (P-gp), or strong inhibitors or inducers of CYP450 isozyme 2C8 (CYP2C8) within 7 days or 5 half-lives prior to the first dose of GLB-001, whichever is shorter prior to the first dose of GLB-001.

• Study participants who have undergone major surgery within 28 days prior to the first dose of the GLB-001, or unability to recover from effects of surgery.

• Pregnant or lactating women.

• Study participants who have cognitive impairment due to any psychiatric or neurological condition, including epilepsy and dementia, may limit their understanding, performance, and study compliance with the ICF.

• Study participants, in the opinion of the Investigator, who are unsuitable to participate in the study.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Essential Thrombocythemia
• Myelodysplastic Syndromes
• Myelofibrosis
• Myeloid Malignancy
• Neoplasms
• Polycythemia
• Polycythemia Vera
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• GLB-001
Administered orally according to the assigned treatment schedule

Locations

Country	Name	City	State
China	China-Japan Friendship Hospital	Beijing	Beijing
China	The First Affilicated Hospital, Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The First Hospital of Hebei Medical Universtiy	Shijia Zhuang	Hebei
China	Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin
China	The Second Hospital of Tianjin Medical Universtiy	Tianjin	Tianjin
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Hangzhou GluBio Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting Toxicity (DLT)	DLT is defined as the treatment emergent adverse events (TEAEs) meeting protocol specified DLT criteria and occurring within the DLT assessment period.	Up to 35 days after first dose of study treatment in Phase 1a and Phase 1b
Primary	Maximum Tolerated Dose (MTD)	MTD is defined as the highest dose level at which no more than 1 of 6 DLT-evaluable study participants experienced a DLT.	Up to 1 year in Phase 1a and Phase 1b
Primary	Recommended Expansion Doses (RED)	RED will be determined by the safety review committee (SRC) according to the safety, tolerability, PK, PD, and preliminary efficacy of GLB-001 in dose escalation phase and dose exploration phase.	Up to 1 year in Phase 1a and Phase 1b
Primary	Incidence, Relatedness, Seriousness and Severity of Adverse Events (AEs)	AE is any untoward medical occurrence in a study participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. AE will be graded according to the National Cancer Institute Common Terminology Criteria for AE (NCI CTCAE) version 5.0.	Up to 3 years in Phase 1a and Phase 1b
Primary	Recommended Phase 2 Dose (RP2D)	RP2D based on the totality of data across dosing cohorts in the dose escalation, dose exploration and dose expansion phases of the study including PK, PD, safety and efficacy outcomes.	Up to 1 year in Phase 1c
Primary	Response Assessment in Study Participants With PV	Response will be evaluated according to the European Leukemia Net (ELN) and 2013 International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria, including overall response rate (ORR), duration of remission or response (DOR), time to response (TTR), progression-free survival (PFS), percentage of study participants who achieved complete hematologic response (CHR), duration of CHR, percentage of study participants with hematocrit (HCT) <45%, percentage of study participants with >50% change in Myeloproliferative Neoplasm Symptom Assessment Total Symptom Score (MPN-SAF TSS), percentage of study participants who achieve spleen volume reduction of greater than or equal to 35% (SVR35) from baseline, duration of SVR35 (DoMSR), change from baseline of JAK2 mutated allele burden.	Up to 3 year in Phase 1c
Primary	Response Assessment in Study Participants With ET	Response will be evaluated according to ELN and 2013 IWG-MRT criteria, including ORR, DOR, TTR, PFS, percentage of study participants who achieved CHR, duration of CHR, percentage of study participants with >50% change in MPN-SAF TSS, percentage of study participants who achieve SVR35 from baseline, DoMSR, change from baseline of JAK2 mutated allele burden.	Up to 1 year in Phase 1c
Primary	Response Assessment in Study Participants With MF	Response will be evaluated according to the European Myelofibrosis Network (EUMNET) and 2013 IWG-MRT criteria, including ORR, DOR, TTR, PFS, percentage of study participants who achieve anemia response, percentage of study participants with symptom response, percentage of study participants who achieve SVR35 from baseline, DoMSR, change from baseline of JAK2 mutated allele burden.	Up to 1 year in Phase 1c
Primary	Response Assessment in Study Participants With LR-MDS	Response will be evaluated according to the 2006 Myelodysplastic Syndromes International Council for Harmonisation (MDS-IWG) criteria, including percentage of study participants with hematology improvement (HI) (erythroid/platelet/neutrophil responses), percentage of study participants with complete response (CR), partial response (PR) or marrow complete response (mCR), DOR, TTR, PFS, percentage of study participants who achieve red blood cell transfusion independence (RBC-TI) = 8 weeks, time to RBC-TI and duration of RBC-TI for study participants who achieve RBC TI = 8 weeks on treatment.	Up to 1 year in Phase 1c
Primary	Response Assessment in Study Participants With HR-MDS	Response was evaluated according to the 2006 MDS-IWG criteria, including HI (erythroid/platelet/neutrophil responses), percentage of study participants with CR, PR or mCR, DOR, TTR, PFS, minimal residual disease (MRD) monitoring in participants who achieve CR.	Up to 1 year in Phase 1c
Primary	Response Assessment in Study Participants With AML	Response was evaluated according to the 2022 ELN for AML criteria, including CR, CR with incomplete hematologic recovery (CRi), CR with partial hematological recovery (CRh), morphologic leukemia-free state (MLFS), percentage of study participants with PR, DOR, TTR, event-free survival (EFS), MRD monitoring in study participants who achieve CR/CRi/CRh.	Up to 1 year in Phase 1c
Secondary	GLB-001 and GLB-C183-A-2 (diastereoisomer of GLB-001) Pharmacokinetics after Single Administration - AUC0-last	Area under the concentration-time curve from zero to the last measurable concentration.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - AUC0-24	Area under the concentration-time curve from 0 to 24 hours.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - AUC0-inf	Area under the concentration-time curve from 0 to infinity.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Cmax	Maximum plasma concentration.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Tmax	The time to reach maximum concentration.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - T1/2	Terminal half-life.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Vz/F	Apparent volume of distribution.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - CL/F	Apparent total clearance of the drug from plasma after oral administration.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - ?z	Terminal rate constant.	Up to 48 hours after single administration
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Tmax,ss	Time of maximum concentration at steady state.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Cav,ss	Average plasma concentration at steady state.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Cmax,ss	Maximum plasma concentration at steady state.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Cmin,ss	Minimum plasma concentration at steady state.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - AUC0-tau	Area under the concentration-time curve during the dosing interval.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration-AUC0-last	Area under the concentration-time curve from zero to the last measurable concentration.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - ?z	Terminal rate constant.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Vz/F	Apparent volume of distribution.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - CLss/F	Apparent clearance at steady state.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - T1/2	Terminal half-life.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Rac [AUC]	Accumulation index in area under the concentration-time curve.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Rac [Cmax]	Accumulation index in maximum plasma concentration.	Up to 1 year
Secondary	GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration-DF	Degree of fluctuation index.	Up to 1 year