Clinical trial NCT03664297: Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrent Replased/Refractory Mature B Cell Neoplasmstumor
Official title: Phase 1 Study to Evaluate the Tolerance and Pharmacokinetics of SHR1459 in Patients With Recurrentreplased/Refractory Mature B Cell Neoplasms Tumor
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Mature B Cell Neoplasms
Keywords: replased/refractory mature B cell neoplasms
BTK inhibitor
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-09-10
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: SHR1459 is a selective small molecule BTK inhibitor developed by Jiangsu Hengrui medicine Limited, by inhibiting the phosphorylation of BTK and down regulation of BCR signal transduction pathway, And then selectively inhibit the proliferation and migration of B cell tumor.

Detailed description: SHR1459 is a selective small molecule BTK inhibitor developed by Jiangsu Hengrui medicine Limited, by inhibiting the phosphorylation of BTK and down regulation of BCR signal transduction pathway, And then selectively inhibit the proliferation and migration of B cell tumor. The objective of this phase 1 study is to evaluate the safety and tolerance of SHR1459 in patients with replaced/refractory mature B cell neoplasms, in order to determine the maximum tolerated dose (MTD) and recommended dose for phase 2 clinical study (RP2D);

Eligibility criteria: Inclusion Criteria:

* ECOG Performance Status \[PS\] score must be 0 or 1;
* Life expectancy ≥ 12 weeks;
* Mature B cell eoplasmss with histological or cytological diagnosis, including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) , chronic lymphocytic leukemia/Small lymphocytic lymphoma (CLL/SLL), Mantle cell lymphoma (MCL), Marginal zone lymphoma (MZL) and waldenstrom macroglobulinemia (WM);
* The function of bone marrow is basically normal;
* Renal function is basically normal;
* Hepatic function is basically normal.

Exclusion Criteria:

* Had received treatment with the compound of the same mechanism (BTK inhibitor);
* With infiltration of lymphoma central nervous system;
* Received autologous stem cell transplantation within 60 days before signing the informed consent, received allogeneic stem cell transplantation in 90 days (after allogeneic stem cell transplantation, if graft-versus-host disease appeared, it must be ≤ level 1, and if there was no prohibited medication, the screening could be performed);

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability])
timeFrame: through study completion, an average of about 6 months
measure: Recommended phase 2 dose (RP2D)
timeFrame: 28 days since the date of first dose
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: every 8 weeks through study completion, an average of about 6 months
measure: Duration of Response (DoR)
timeFrame: every 8 weeks through study completion, an average of about 6 months
measure: Progression-free survival (PFS)
timeFrame: every 8 weeks through study completion, an average of about 6 months
measure: Time to Response (TTR)
timeFrame: every 8 weeks through study completion, an average of about 6 months
measure: Time to peak (Tmax)
timeFrame: Day 1 and Day 2 of the single dose
measure: Maximum plasma concentration (Cmax)
timeFrame: Day 1 and Day 2 of the single dose
measure: Halflife (T1/2)
timeFrame: Day 1 and Day 2 of the single dose
measure: Clearance/ bioavailability (CL/F)
timeFrame: Day 1 and Day 2 of the single dose
measure: apparent volume of distribution/bioavailability (Vd/F)
timeFrame: Day 1 and Day 2 of the single dose
measure: Area under curve (AUC)
timeFrame: Day 1 and Day 2 of the single dose
measure: Area under curve, steady state (AUCss)
timeFrame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
measure: Maximum plasma concentration, steady state (Cmax,ss)
timeFrame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
measure: Time to peak, steady state (Tmax,ss)
timeFrame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
measure: Halflife (T1/2)
timeFrame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
measure: Apparent volume of distribution, steady state/bioavailability (Vss/F)
timeFrame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
measure: Clearance/ bioavailability (CL/F)
timeFrame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
measure: Accumulation index (Rac)
timeFrame: Day 1 of cycle 1 to day 1 of cycle 4 (28 days/cycle)
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Blood disease hospital of Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Blood Institute of the Chinese Academy of Medical Sciences
name: Lugui Qiu
role: PRINCIPAL_INVESTIGATOR
References: