SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00802841

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Randomized Phase Lll Study of Imatinib Dose Optimization Compared With Nilotinib in Patients With Chronic Myelogenous Leukemia and Suboptimal Response to Standard-dose Imatinib

There is no available data on the clinical benefit of dose escalation for patients with suboptimal response to imatinib, and patients may still improve their response with continuation of therapy at the standard dose as shown in the IRIS trial after 5 years of follow-up. However, there is no data yet regarding the potential benefit of using nilotinib in the group of patients with suboptimal response. In this study, the efficacy of nilotinib 400mg BID will be compared to imatinib 600mg QD.

NCT00802841 Chronic Myelogenous Leukemia
MeSH: Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Chronic myelogenous leukemia Leukemia Myeloid leukemia

2 Interventions

Name: nilotinib

Description: Supplied as 200 mg tablets

Type: Drug

Nilotinib

Name: imatinib

Description: Supplied as 100 mg and 400 mg tablets

Type: Drug

Imatinib


Primary Outcomes

Description: CCyR was assessed from bone marrow samples. CCyr was defined as having 0% Philadelphia positive (Ph+) chromosome metaphases in bone marrow.

Measure: Percentage of Participants With Complete Cytogenetic Response (CCyR)

Time: 6 months

Secondary Outcomes

Description: MMR was defined as having a fusion gene of the Bcr and Abl genes of (BCR-ACL) less than or equal to 0.1% on the International Scale (IS).

Measure: Percentage of Participants With Major Molecular Response (MMR)

Time: 12 and 24 months

Description: CCyR was assessed from bone marrow samples. CCyr was defined as having 0% Philadelphia positive (Ph+) chromosome metaphases in bone marrow.

Measure: Percentage of Participants With CCyr

Time: 12 and 24 months

Description: Time to CCyR was defined as time from date of randomization to date of first documented CCyR.

Measure: Time to CCyR

Time: 24 months

Description: Duration of CCyR was defined as time from the date of ransomization to the date of first loss of CCyR or death, whichever came first.

Measure: Duration of CCyR

Time: 24 months

Description: PFS was defined as the time from the date of randomization to the date of documented disease progression to accelerated phase or blast crisis (AP/BC), or death due to any cause.

Measure: Progression-Free Survival (PFS)

Time: 24 months

Description: EFS was defined as the time from the date of randomization to the date of the first occurrence of any of the following: loss of Complete Hematological Response (CHR), loss of Partial Cytogenetic Response (PCyR), loss of CCyR, death on treatment or progression to AP/BC.

Measure: Event-Free Survival (EFS)

Time: 24 months

Description: OS was defined as time from date of randomization to the date of the death.

Measure: Overall Survival (OS)

Time: 24 months

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 T315I

Exclusion criteria: 1. Prior accelerated phase including clonal evolution or blast crisis CML; 2. Prior therapy with imatinib in combination with any other CML drug other than Hydroxyurea and/or Anagrelide; 4.Imatinib therapy started more than 12 months after the date of the original diagnosis; 5.Unable to tolerate imatinib at 400mg; 6.Previous treatment with any other tyrosine kinase inhibitor except Glivec and/or CML therapy other than IFN, hydroxyurea, and /or anagrelide; 7.Myelotoxicity ≥ Grade 2 present at the time of randomization, 8.Previously documented T315I mutations; 9.Impaired cardiac function including one of these: - Long QT syndrome or family history of long QT syndrome - Clinically significant resting brachycardia (<50 bpm) - QTcF >450 msec on screening ECG (using the QTcF formula). --- T315I ---



HPO Nodes


HPO:
Chronic myelogenous leukemia
Genes 5
MPL BCR JAK2 KIT THPO
Leukemia
Genes 125
MPL RNASEH2B KRAS NPM1 TET2 MYD88 TSR2 RPL26 RPL27 TREX1 EFL1 PIGL SCN11A FLT3 PMS2 RPL35A EVC2 ABL1 CEBPA RARA NRAS WAS WIPF1 ATRX SH2B3 PDGFRA RB1 RNASEH2A PDGFRB CALR ARHGAP26 SH3GL1 RPS7 RPS10 NUMA1 GATA1 GATA2 RPS15A APC NSD1 ETV6 TCIRG1 DNAJC21 EVC SRP54 RPS17 NBN RPS19 SAMHD1 MSH2 RPS24 NUP214 RPS26 RPS27 RPS28 RPS29 MLLT10 RUNX1 XRCC4 CBFB CBL BCR ADAR TRIP13 ADA2 NSUN2 CREBBP PICALM GFI1 F13A1 F13B FANCA FANCC BLM FANCD2 FANCE NUTM1 JAK2 IFIH1 TYROBP MSH6 FANCG LIG4 PTPN11 SAMD9L THPO NF1 STS PIGA BRCA2 DYNC2LI1 PIK3CA SBDS GLI1 PIK3R1 BRD4 SETBP1 RNASEH2C LPP BUB1 BUB1B SCN9A SCN10A TREM2 MLF1 MLH1 ELANE DKC1 ATM HAX1 RPL35 GNB1 BUB3 CEP57 TAL1 KIT TAL2 RPL5 EP300 TP53 RPL11 KIF11 RPL15 DNMT3A RPL18
Myeloid leukemia
Genes 12
GATA2 F13A1 CBL ARHGAP26 F13B KRAS PTPN11 SAMD9L KIT SETBP1 NF1 NRAS