SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT03357627

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1b Study of TAK-659 in Combination With Venetoclax for Adult Patients With Previously Treated Non-Hodgkin Lymphoma

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of TAK-659 and venetoclax when administered in combination in participants with non-Hodgkin lymphoma (NHL) relapsed and/or refractory after at least 1 prior line of therapy and to evaluate safety and tolerability of TAK-659 and venetoclax when administered in combination.

NCT03357627 Lymphoma, Non-Hodgkin Lymphoma, Large B-cell, Diffuse Lymphoma, Follicular
MeSH: Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Large B-Cell, Diffuse Lymphoma, Follicular
HPO: Lymphoma Non-Hodgkin lymphoma

2 Interventions

Name: TAK-659

Description: TAK-659 tablets.

Type: Drug

Dose Escalation: TAK-659 + Venetoclax Safety Expansion: Diffuse Large B-cell Lymphoma (DLBCL) Cohort Safety Expansion: Follicular Lymphoma (FL) Cohort

Name: Venetoclax

Description: Venetoclax tablets.

Type: Drug

Dose Escalation: TAK-659 + Venetoclax Safety Expansion: Diffuse Large B-cell Lymphoma (DLBCL) Cohort Safety Expansion: Follicular Lymphoma (FL) Cohort


Primary Outcomes

Description: Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE), Version 5.0 DLT will be defined as any of the events specified in the protocol that are considered by the investigator to be at least possibly related to therapy with study medications and that occur within the first cycle.

Measure: Number of Participants with a Dose Limiting Toxicity (DLT)

Time: Baseline up to 5 weeks

Description: AE Grades will be evaluated as per NCI CTCAE, version 5.0.

Measure: Percentage of Participants Reporting one or More Treatment-emergent Adverse Events (TEAEs), Grade 3 or Higher Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Discontinuation

Time: Baseline up to 13 months

Secondary Outcomes

Measure: Cmax: Maximum Observed Plasma Concentration for TAK-659 and Venetoclax

Time: Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length is equal to [=] 35 days)

Measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 and Venetoclax

Time: Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)

Measure: AUCĪ„: Area Under the Plasma Concentration-time Curve from Time 0 to Time Over the Dosing Interval for TAK-659 and Venetoclax

Time: Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)

Measure: Oral Clearance (CL/F) for TAK-659 and Venetoclax

Time: Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)

Measure: Peak-trough Ratio (PTR) for TAK-659 and Venetoclax

Time: Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)

Measure: Accumulation Ratio (Rac) for TAK-659 and Venetoclax

Time: Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)

Measure: Trough Concentration (C trough) for TAK-659 and Venetoclax

Time: Cycle 1 Days 1 and 21 or 28: Pre-dose and at multiple time points (up to 24 hours) post-dose (Cycle length =35 days)

Description: ORR is calculated as percentage of participants with complete response (CR) + percentage of participants with partial response (PR) as assessed by International Working Group (IWG) criteria for malignant lymphoma.

Measure: Overall Response Rate (ORR)

Time: Up to 12 months

Measure: Duration of Overall Response

Time: Up to 12 months

Description: CR rate is calculated as percentage of participants with CR as assessed by IWG criteria for malignant lymphoma.

Measure: CR Rate

Time: Up to 12 months

Measure: Duration of CR

Time: Up to 12 months

Description: TTP will be measured as the time in months from the first dose of study treatment to the date of the first documented disease progression as assessed using IWG criteria.

Measure: Time to Progression (TTP)

Time: Up to 13 months

Description: PFS is defined as the time from date of first study drug administration to the day of first documented disease progression or death due to any cause, whichever occurs first.

Measure: Progression-free Survival (PFS)

Time: Up to 18 months

Purpose: Other

Allocation: Non-Randomized

Sequential Assignment


There is one SNP

SNPs


1 P4503A

Use or consumption of: - Medications or supplements that are known to be strong or moderate Cytochrome P4503A (CYP3A) inhibitors or strong or moderate CYP3A inducers and/or P-glycoprotein (P-gp) inhibitors or inducers within 7 days or within 5 times the inhibitor or inducer half-life (whichever is longer) before the first dose of study drugs. --- P4503A ---



HPO Nodes


HPO:
Lymphoma
Genes 133
ATM KRAS CD19 IGH DDX41 BCL10 BIRC3 FOXP1 MS4A1 TP63 RAG1 LIG4 NFKB2 MSH6 TERC RECQL4 NTHL1 WIPF1 CTC1 LYST NOP10 RASGRP1 TNFRSF1B XRCC4 PRKCD NHP2 MAGT1 TNFRSF13B IGH RMRP RUNX1 CTLA4 DCLRE1C FAS ICOS RNF43 NSUN2 XIAP IL7R CASP10 BCL6 CDKN2A ATM IL2RG RTEL1 PARN NBN KIT TNFRSF13C TCF4 ICOS TNFSF12 CHEK2 USB1 CD19 CR2 NRAS MSH2 WAS BCL10 CASP10 MYD88 COL14A1 PRKCD TNFRSF13B MYC MDM2 SH2D1A CCND1 BCL10 CFTR CD27 PGM3 TCF4 CHD7 IGH LIG4 BLM BCL2 TET2 HLA-DRB1 PRSS1 NPM1 KIF11 ITK WRAP53 RAD54B TINF2 FAS DKC1 APC CD81 LIG4 BLM CD28 DKC1 AAGAB RAG2 TNFRSF1B MLH1 TNFRSF13C DNASE1L3 NFKB1 PMS2 ASXL1 IL2RG PRF1 PTEN MALT1 RAD54L CTLA4 CD28 PNP SRSF2 TNFSF12 STAT3 POLE ADA CR2 ADA FASLG PIK3R1 TP53 CTRC ZAP70 MYD88 RB1 RMRP SPINK1 TERT KLHDC8B NBN RHOH
Non-Hodgkin lymphoma
Genes 32
ATM FAS CASP10 CTLA4 FAS BCL10 CD28 BIRC3 FOXP1 TNFRSF1B MYC CCND1 ASXL1 ATM MALT1 CTLA4 CD28 SRSF2 KIT POLE IGH ADA TET2 FASLG PIK3R1 NTHL1 RASGRP1 TNFRSF1B PRKCD NBN RHOH IGH