Study of APG2575 Single Agent and Combination Therapy in Patients With Relapsed/Refractory CLL/SLL
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorAscentage Pharma Group Inc.
About this trial
The purpose of this study is to assess the safety, pharmacokinetic, pharmacodynamic and efficacy of APG-2575 single agent and in combination with other therapeutic agents in patients with relapsed/refractory CLL/SLL.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥18 years old.
Diagnosis as relapsed/refractory chronic lymphocytic leukemia/ small lymphocytic lymphoma according to the IWCLL NCI-WG guidelines revised in 2008.
Through radiological assessment, subjects with a lymph node length ≥ 10 cm require prior approval from the sponsor before enrollment.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS): 0 -1.
Disqualifiers
Prior history of allogeneic hematopoietic stem cell transplantation, adoptive cell immunotherapy within 24 months or autologous hematopoietic stem cell transplantation within 12 months.
Monoclonal antibody therapy against CLL was adopted within 4 weeks prior to the first dose of the study drug.
Receive any of the following treatments within 14 days or 5x half-life before the first dose of study drug, or clinically significant adverse reactions / toxicities due to previous treatments have not recovered to ≤ Grade 1: Anti-tumor therapies include chemotherapy, radiotherapy, anti-tumor steroid treatment, anti-tumor Chinese medicine treatment; investigational treatment, including targeted small molecule drugs.
Use the following drugs within 14 days before the first dose of study drug: moderately potent CYP3A inhibitors such as fluconazole, ketoconazole and clarithromycin; moderately potent CYP3A inducers such as rifampin, carbamazepine, phenytoin And St. John's wort.
Trial design
Design model
Parallel
Treatments tested in this trial
APG-2575
DrugAPG-2575 orally once daily, every 28 days as a cycle.
Rituximab
DrugRituximab 375mg/m2 ivgtt on C1D8 and 500mg/m2 ivgtt on C2-6D1.
Ibrutinib
DrugIbrutinib 420mg orally once daily during C1D8-28 and following cycles.
Treatment groups
123 Participants
are divided into 3 treatment groupsGroup A: APG-2575 single agent in Relapse/Refractory CLL/SLLExperimental treatment 1 intervention
Group B: APG-2575+Rituximab in Relapse/Refractory CLL/SLLExperimental treatment 2 interventions
Group C: APG-2575+ibrutinib in Relapse/Refractory CLL/SLLExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Adverse events of APG-2575 single agent
Adverse events (AE) and serious adverse events (SAE) will be graded according to NCI CTCAE Version 5.0.
Time frame
Up to 6 cycles (each cycle is 28 days).2
Objective Response Rate (ORR) of APG-2575 single agent
ORR is defined by CR+ CRi + PR(according to NCI-WG CLL(2008)) and by CR+PR ( according to NHL Cheson (2007)).Response will be evaluated every 2 cycles (8 weeks) till complete 6 cycles treatment or one month after last dose.
Time frame
Up to 6 cycles (each cycle is 28 days).3
Dose Limiting Toxicities (DLT) of combination therapy
DLT will be graded according to NCI CTCAE Version 5.0. DLT will be defined as clinically significant drug-related adverse events during the cycle one.
Time frame
28 days.4
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose(RP2D)
MTD/RP2D will be determined based on DLTs observed during cycle one.
Time frame
28 days.Secondary outcomes
1
Maximum plasma concentration (Cmax)
Cmax of APG-2575 will be assessed in the patients in single agent or combo study. Cmax of ibrutinib will be assessed in the patients treated with APG-2575 combination with ibrutinib.
Time frame
28 days.2
Area under the plasma concentration versus time curve (AUC)
AUC of APG-2575 will be assessed in the patients in single agent or combo study. AUC of ibrutinib will be assessed in the patients treated with APG-2575 combination with ibrutinib.
Time frame
28 days.3
Objective Response Rate (ORR) of APG-2575 combination therapy
ORR is defined by CR+ CRi + PR(according to NCI-WG CLL(2008)) and by CR+PR ( according to NHL Cheson (2007)).Response will be evaluated every 2 cycles (8 weeks) till complete 6 cycles treatment or one month after last dose.
Time frame
Up to 6 cycles (each cycle is 28 days).4
Minimal residual lesions (MRD) of peripheral blood and/or bone marrow.
Time frame
2 years.Sponsors and contacts
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Source ClinicalTrials.gov