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Report for Clinical Trial NCT02117336

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I/Ib Study of P1446A-05 in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL).

This is an open-label, Phase I/Ib trial with a dose escalation phase, followed by a dose extension phase. The objective of the dose escalation phase is to evaluate the pharmacokinetics (PK) and MTD of P1446A-05 in relapsed/refractory CLL and the objective of the dose extension phase is to evaluate the safety, efficacy and pharmacodynamics of P1446A-05 in 14 patients at the MTD level.

NCT02117336 Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
MeSH: Leukemia Leukemia, Lymphoid Leukemia, Lymphocytic, Chronic, B-Cell
HPO: Chronic lymphatic leukemia Leukemia Lymphoid leukemia

1 Interventions

Name: P1446A-05

Description: The study have dose escalation phase, followed by a dose extension phase. Dose escalation phase: five Dose Levels will be evaluated in the 'dose escalation' phase. The Dose Levels selected are 50 mg (Dose Level 1), 75 mg (Dose Level 2), 125 mg (Dose Level 3), 200 mg (Dose Level 4) and 275 mg (Dose Level 5), once daily. If required, a 25 mg once daily dose (Dose Level -1) will also be studied. For Dose Levels 1, 2 and 3 there will be 2- dosing periods: Single Dose and Continuous Dose. At least 3-patients will be enrolled at each Dose Level. Dosing regimens planned for Dose Level 4 and 5 are 200 and 275 mg once daily. In the continuous dose period, patients will receive P1446A-05 on a 28-day cycle, until the occurrence of disease progression or unacceptable toxicity. Dose Extension Phase: Up to a total of 14 patients will be treated at the MTD of P1446A-05, determined in the dose escalation phase, until the occurrence of disease progression or unacceptable toxicity or death.

Type: Drug

P1446A-05


Primary Outcomes

Description: To establish maximum tolerated dose (MTD) of P1446A 05 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). There will be two phase, a dose escalation phase, followed by a dose extension phase. In the 'dose extension phase', up to a total of 14 patients will be treated at the MTD of P1446A-05, determined in the 'dose escalation' phase, until the occurrence of disease progression or unacceptable toxicity or death

Measure: Maximum Tolerated Dose

Time: Cycle 1 (Day 1 to 28 )

Description: To establish dose limiting toxicities (DLTs) of P1446A 05 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). - There will be two phase, a dose escalation phase, followed by a dose extension phase.

Measure: Dose Limiting Toxicity

Time: Cycle 1 (Day 1 to 28 )

Secondary Outcomes

Description: To determine the efficacy (overall response ) of P1446A 05 in patients with relapsed/refractory CLL. Overall Response will be assessed according to IWCLL 2008 criteria. Kaplan-Meier curve of overall survival will also be presented. OS will be evaluated in the dose extension phase only.

Measure: Overall response

Time: At the end of every 2 cycles,Until disease progression or unacceptable toxicity (average of 2years)

Description: To determine the efficacy (progression-free survival) of P1446A 05 in patients with relapsed/refractory CLL. Kaplan-Meier estimates of progression-free survival i.e. median and inter-quartile range will be presented. Kaplan-Meier curve of overall survival will also be presented. OS will be evaluated in the dose extension phase only.

Measure: Progression-free survival

Time: At the end of every 2 cycles, until disease progression or unacceptable toxicity (average of 2years)

Description: Samples for pharmacokinetic analysis for PK profile (Cmax,Tmax and AUC) will be collected on S-D1at pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 h post on Day S-D1 of single dose period (for Dose Levels 1, 2 and 3). In the continuous dose period, samples will be collected on Day 28 of Cycle 1 at pre-dose, and at 0.5, 2, 4, 6, 8 and 24 h post-dose. Additional samples will be collected pre dose on Day 15 and 22 of Cycle 1 to monitor the attainment of steady state. Pre-dose samples will also be collected on C2D15, C2D28, C3D15, C3D28 and C5D1. PK parameters will be obtained using standard non-compartmental methods. PK evaluations will not be performed in the dose extension phase. Descriptive statistics will be provided for the PK parameters. The PK analysis will be performed using WinNonlin software

Measure: Pharmacokinetic profile (Cmax,Tmax and AUC)

Time: SD1, Cycle1-Cycle 5 (average of 5 month)

Other Outcomes

Description: To assess whether established (IGHV, p53 and Notch mutational status and ZAP70 and CD38 expression,) and exploratory biomarkers (e.g. expression levels of Cyclin D1, p53 etc.) predict response to P1446A-05 in relapsed/refractory CLL

Measure: Biomarker Analysis

Time: Cycle1Day1, Cycle1Day28, Until disease progression or unacceptable toxicity (average of 2years)

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 P1446A

A Phase I/Ib Study of P1446A-05 in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL).. Clinical Study of Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) This is an open-label, Phase I/Ib trial with a dose escalation phase, followed by a dose extension phase. --- P1446A ---

The objective of the dose escalation phase is to evaluate the pharmacokinetics (PK) and MTD of P1446A-05 in relapsed/refractory CLL and the objective of the dose extension phase is to evaluate the safety, efficacy and pharmacodynamics of P1446A-05 in 14 patients at the MTD level. --- P1446A ---

The objective of the dose escalation phase is to evaluate the pharmacokinetics (PK) and MTD of P1446A-05 in relapsed/refractory CLL and the objective of the dose extension phase is to evaluate the safety, efficacy and pharmacodynamics of P1446A-05 in 14 patients at the MTD level. --- P1446A --- --- P1446A ---

To establish maximum tolerated dose (MTD) of P1446A 05 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). --- P1446A ---

In the 'dose extension phase', up to a total of 14 patients will be treated at the MTD of P1446A-05, determined in the 'dose escalation' phase, until the occurrence of disease progression or unacceptable toxicity or death. --- P1446A ---

To establish dose limiting toxicities (DLTs) of P1446A 05 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). --- P1446A ---

To determine the efficacy (overall response ) of P1446A 05 in patients with relapsed/refractory CLL. --- P1446A ---

To determine the efficacy (progression-free survival) of P1446A 05 in patients with relapsed/refractory CLL. --- P1446A ---

expression levels of Cyclin D1, p53 etc.) predict response to P1446A-05 in relapsed/refractory CLL. --- P1446A ---

P1446A-05 is both highly protein bound and a competitive inhibitor of CYP2C9 at higher concentrations and thus may potentiate the action of warfarin in patients 10. --- P1446A ---



HPO Nodes


HPO:
Chronic lymphatic leukemia
Genes 8
ADAR TREX1 IFIH1 PIK3R1 RNASEH2A SAMHD1 RNASEH2B RNASEH2C
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Lymphoid leukemia