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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
108
Administered orally according to the assigned treatment schedule
The First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital)
Hefei, Anhui, China
RECRUITINGChina-Japan Friendship Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
RECRUITINGThe First Hospital of Hebei Medical Universtiy
Shijiazhuang, Hebei, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGZhongnan Hospital of Wuhan University
Wuhan, Hubei, China
RECRUITINGThe First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGThe First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, China
RECRUITINGSheng Jing Hospital of China Medical Universtiy
Shenyang, Liaoning, China
RECRUITINGHuashan Hospital Affiliated to Fudan University
Shanghai, Shanghai Municipality, China
RECRUITING...and 4 more locations
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.
Time frame: Up to 28 days after first dose of study treatment in Phase 1a and Phase 1b
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.
Time frame: Up to 1 year in Phase 1a and Phase 1b
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.
Time frame: Up to 1 year in Phase 1a and Phase 1b
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.
Time frame: Up to 3 years in Phase 1a and Phase 1b
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.
Time frame: Up to 1 year in Phase 1c
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.
Time frame: Up to 3 year in Phase 1c
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.
Time frame: Up to 1 year in Phase 1c
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.
Time frame: Up to 1 year in Phase 1c
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.
Time frame: Up to 1 year in Phase 1c
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.
Time frame: Up to 1 year in Phase 1c
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.
Time frame: Up to 1 year in Phase 1c
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.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - AUC0-24
Area under the concentration-time curve from 0 to 24 hours.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - AUC0-inf
Area under the concentration-time curve from 0 to infinity.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Cmax
Maximum plasma concentration.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Tmax
The time to reach maximum concentration.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - T1/2
Terminal half-life.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - Vz/F
Apparent volume of distribution.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - CL/F
Apparent total clearance of the drug from plasma after oral administration.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Single Administration - λz
Terminal rate constant.
Time frame: Up to 48 hours after single administration
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Tmax,ss
Time of maximum concentration at steady state.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Cav,ss
Average plasma concentration at steady state.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Cmax,ss
Maximum plasma concentration at steady state.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Cmin,ss
Minimum plasma concentration at steady state.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - AUC0-tau
Area under the concentration-time curve during the dosing interval.
Time frame: Up to 1 year
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.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - λz
Terminal rate constant.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Vz/F
Apparent volume of distribution.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - CLss/F
Apparent clearance at steady state.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - T1/2
Terminal half-life.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Rac [AUC]
Accumulation index in area under the concentration-time curve.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration - Rac [Cmax]
Accumulation index in maximum plasma concentration.
Time frame: Up to 1 year
GLB-001 and GLB-C183-A-2 Pharmacokinetics after Multiple Administration-DF
Degree of fluctuation index.
Time frame: Up to 1 year