This is a single-arm and open-label study to explore X+MTX+Ritu (ATG-010, Methotrexate, Rituximab) regimen in Relapse refractory PCNSL patients. Approximately 30 patients will be enrolled in the study. In dose escalation phase, patients with Relapse refractory PCNSL will be treated with X+MTX+Ritu regimen and escalating doses of oral ATG-010 weekly in a 3+3 design. Then a phase 2 expansion at the recommended dose level based on phase 1b trial will be conducted to evaluate the efficacy, safety and tolerability.
In dose escalation phase, patients with Relapse refractory PCNSL will be treated with X+MTX+Ritu regimen (Methotrexate 3.5 g/m2, d1; Rituximab 375 mg/m2, d0)and escalating doses of oral ATG-010 weekly in a 3+3 design. ATG-010 dose level (DL) 1, 2 and 3 are 60, 80 and 100mg respectively respectively on day 1,8,15,22 for 28-days cycle. The phase 2 expansion at the recommended dose level based on phase 1b trial. The total 6 cycles, 28 days per cycle . And, Subjects participating in the study will undergo a screening period(up to 21days), a treatment period, and a follow-up period. The screening period is a maximum of 21 days before treatment period, And will be followed by 6 cycles of combination treatment(28 days per cycle). partial remission(PR) patients after induction treatment will continue ATG-010 maintenance up to 1 year or until disease progression, intolerable toxicity, death.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Selinexor dose escalation: 60,80,100mg respectively on day 1,8,15,22 for 28 days cycles, and dose expansion at the RP2D of Selinexor. PR patients after induction treatment will continue ATG-010 maintenance up to 1 year or until disease progression, intolerable toxicity, death.
Rituximab 375 mg/m2 intravenous infusion d1, every 28 days for 6 cycles during combination induction treatment.
high-dose Methotrexate 3.5 g/m2 intravenous infusion d1, every 28 days for 6 cycles during combination induction treatment.
The First Affiliated Hospital Of Anhui Medical University
Hefei, Anhui, China
NOT_YET_RECRUITINGBeijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
NOT_YET_RECRUITINGThe First Affiliated Hospital Of Fujian Medical University
Fuzhou, Fujian, China
Dose Escalation: Maximum Tolerated Dose (MTD) of Selinexor
The MTD will be determined by study definition as the highest dose level without significant safety and tolerability concern.
Time frame: Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days)
Dose Escalation: Recommended Phase 2 Does (RP2D) of Selinexor
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy data collected during the dose escalation portion of the study
Time frame: Assessed from the date of first dose of study treatment to the first cycle ends (maximum 21days)
Objective Response Rate (ORR)
ORR is defined as the proportion of patients with a best response of Complete remission (CR) or Unconfirmed(CRu), or PR during induction therapy
Time frame: Cycle 1 Day 1 (each cycle consists of maximum 21 days) until a CR, CRu or PR (up to 18 cycles(each cycle is 21 days)).
Duration of Response (DOR)
Duration from the first observation of at least PR to time of progressive disease(PD), or deaths due to disease progression,whichever occurs first
Time frame: From first dose of study drug administration to end of treatment, up to 18 cycles(each cycle is 21 days)
Overall Survival (OS)
Occurrence of death regardless of cause
Time frame: up to 12 months
Progression-Free Survival (PFS)
Duration from start of study treatment to PD or death (regardless of cause), whichever comes first
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Oncology Department of The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
NOT_YET_RECRUITINGDepartment of Hematology, Huashan Hospital, Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGTime frame: up to 12 months
Number of Participants with Adverse Events
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Time frame: From first dose of study drug administration to end of treatment (up to 18 cycles(each cycle is 21 days))