This is a multicentre, open-label, single-arm, phase Ib clinical study to evaluate the safety, tolerability, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine and Prednisone in the frontline treatment of patients with peripheral T cell lymphoma (PTCL).
The study is to investigate the safety, tolerability, efficacy and pharmacokinetics of liposomal mitoxantrone hydrochloride in combination with Cyclophosphamide, Vincristine and Prednisone in the frontline treatment of patients with PTCL by conducting in two stages, Dose-finding stage and Dose-expansion stage.In Dose-finding stage, patients with treatment-naïve PTCL will be assigned to receive sequentially higher doses of liposomal mitoxantrone hydrochloride ranging from 12 to 18 mg/m2 plus Cyclophosphamide, Vincristine and Prednisone (28 days per cycle). The dose escalation will follow the classic 3+3 design. The recommended Phase 2 dose (RP2D) of liposomal mitoxantrone hydrochloride will be determined according to the Dose-finding results. In Dose-expansion stage, additional patients will be recruited into two groups, the Q4W group(28 days per cycle)and the Q3W group(21 days per cycle), to receive liposomal mitoxantrone hydrochloride at the RP2D combined with Cyclophosphamide, Vincristine and Prednisone. All patients will receive the treatment for the planned 6 cycles or until disease progression or unacceptable drug-related adverse events.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Drug: Liposomal mitoxantrone hydrochloride (12 mg/m2, 15 mg/m2, 18 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle. Drug: Cyclophosphamide (750 mg/m2) will be administered by an intravenous infusion on day 1 of each 28-day cycle. Drug: Vincristine (1.4 mg/m2 with 2 mg as the maximum dose) will be administered by an intravenous injection on day 1 of each 28-day cycle. Drug: Prednisone (100 mg/d) will be taken orally from day 1 to day 5 of each 28-day cycle.
Drug: Liposomal mitoxantrone hydrochloride (at RP2D) will be administered by an intravenous infusion on day 1 of each 28- or 21-day cycle. Drug: Cyclophosphamide (750 mg/m2) will be administered by an intravenous infusion on day 1 of each 28- or 21-day cycle. Drug: Vincristine (1.4 mg/m2 with 2 mg as the maximum dose) will be administered by an intravenous injection on day 1 of each 28- or 21-day cycle. Drug: Prednisone (100 mg/d) will be taken orally from day 1 to day 5 of each 28- or 21-day.
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
Dose-finding stage: The incidence of dose limited toxicities (DLTs)
To identify the DLTs
Time frame: Cycle 1 (28 days)
Dose-finding stage:The incidence of AE and SAE
To identify the incidence of AE and SAE, abnormalities in clinical laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams
Time frame: up to 24 weeks
Dose-expansion stage: The incidence of AE and SAE
To identify the incidence of AE and SAE, abnormalities in clinical laboratory assessments, ECGs, echocardiography, vital sign assessments, and physical exams
Time frame: up to 18-24 weeks
Dose-finding stage: complete response(CR) rate
To investigate the preliminary antitumor efficacy
Time frame: up to 24 weeks
Dose-finding stage: duration of complete response(DoCR)
To investigate the preliminary antitumor efficacy
Time frame: Throughout study completion,an average of 18 months
Dose-finding stage: overall response rate (ORR)
To investigate the preliminary antitumor efficacy
Time frame: up to 24 weeks
Dose-finding stage: progression-free survival(PFS)
To investigate the preliminary antitumor efficacy
Time frame: Throughout study completion,an average of 18 months
Dose-finding stage:the pharmacokinetic parameters Cmax
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To investigate the PK characteristics
Time frame: Cycle 1 to Cycle 6(each cycle is 28 days)
Dose-finding stage:the pharmacokinetic parameters AUC0-t
To investigate the PK characteristics
Time frame: Cycle 1 to Cycle 6(each cycle is 28 days)
Dose-expansion stage: CR rate
To investigate the preliminary antitumor efficacy
Time frame: up to 24 weeks
Dose-expansion stage: DoCR
To investigate the preliminary antitumor efficacy
Time frame: Throughout study completion,an average of 18 months
Dose-expansion stage: ORR
To investigate the preliminary antitumor efficacy
Time frame: up to 18-24 weeks
Dose-expansion stage: PFS
To investigate the preliminary antitumor efficacy
Time frame: Throughout study completion,an average of 18 months
Dose-expansion stage: the pharmacokinetic parameters Cmax
To investigate the PK characteristics
Time frame: Cycle 1(each cycle is 21or28 days)
Dose-expansion stage: the pharmacokinetic parameters AUC0-t
To investigate the PK characteristics
Time frame: Cycle 1(each cycle is 21or28 days)