Ignite Creation Date:
2024-05-05 @ 4:51 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00327132
Status:
COMPLETED
Last Update Posted:
2016-03-25
First Post:
2006-05-17
Brief Title:
Prospective Study of First-line Antibiotic Therapy for Early-stage Gastric MALT Lymphoma for Treatment Outcome
Sponsor:
National Health Research Institutes Taiwan
Organization:
National Health Research Institutes Taiwan
Study Overview
Official Title:
MulticentreProspective Study of First-line Antibiotic Therapy for Early-stage Low-grade and High-grade Gastric Mucosa-associated Lymphoid Tissue-type Lymphoma and Potential Predicting Factor for Treatment Outcome
Status:
COMPLETED
Status Verified Date:
2016-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
1 The complete histological and molecular remission rate for antibiotics as 1st-line therapy for Hp-positive early-stage gastric lg- and hg-MALT lymphoma
2 The durability of complete histological remission after antibiotics
3 The usefulness of pattern of NF-kB and BCL-10 by IHC staining in prospectively predicting the Hp-dependence of gastric lg- and hg-MALT lymphoma
4 The frequency of t1118 translocation in gastric lg- and hg-MALT lymphoma in Taiwan
5 The association between the CYP2C1819 genetic polymorphisms and eradication of Hp infection after antibiotics
2 The durability of complete histological remission after antibiotics
3 The usefulness of pattern of NF-kB and BCL-10 by IHC staining in prospectively predicting the Hp-dependence of gastric lg- and hg-MALT lymphoma
4 The frequency of t1118 translocation in gastric lg- and hg-MALT lymphoma in Taiwan
5 The association between the CYP2C1819 genetic polymorphisms and eradication of Hp infection after antibiotics
Detailed Description:
Background Eradication of Helicobacter pylori Hp infection is well recognized as the initial therapy for early-stage low-grade gastric mucosa-associated lymphoid tissue-type lymphoma lg-MALT lymphoma On the other hand high-grade transformed MALT lymphoma hg-MALT lymphoma is generally considered to arise from Hp-independent clones and thus to be unlikely to respond to antibiotic therapy Our previous prospective studies have firstly demonstrated that 1st-line antibiotic therapy could achieve durable complete histological remission in two-third of Hp-positive stage IE hg-MALT lymphoma Chen et al J Clin Oncol 2001 in which the long-term clinical outcomes were equivalent to those achievable in lg-MALT lymphoma Chen et al J Natl Cancer Inst accepted In addition our laboratory studies have confirmed that t1118 translocation is associated with loss of Hp-dependence in lg-MALT lymphoma but infrequently found in high-grade tumors We also found that nuclear translocation of NF-kB or BCL-10 by immunohistochemical IHC staining were useful markers to predict the Hp-dependence of both early-stage gastric hg- and lg-MALT lymphoma to antibiotic therapy Kuo et al JCO 2004 Yeh et al Blood 2005 In addition recent data suggested cytochrome CYP2C1819 genetic polymorphisms are associated with the metabolism of omeprazole and thus the genotype of such enzymes might affect the efficacy of antibiotics for eradication of Hp infection
Aims A nationwide study to prospectively validate
1 The complete histological and molecular remission rate for antibiotics as 1st-line therapy for Hp-positive early-stage gastric lg- and hg-MALT lymphoma
2 The durability of complete histological remission after antibiotics
3 The usefulness of pattern of NF-kB and BCL-10 by IHC staining in prospectively predicting the Hp-dependence of gastric lg- and hg-MALT lymphoma
4 The frequency of t1118 translocation in gastric lg- and hg-MALT lymphoma in Taiwan
5 The association between the CYP2C1819 genetic polymorphisms and eradication of Hp infection after antibiotics
Materials and Methods Patients with newly histologically proven stage IE IIE-1 gastric lg- and hg-MALT lymphoma are eligible Pre-treatment Hp infection status will be determined by histology rapid urease test and serology At time of registration patients should agree to provide endoscopic biopsy specimen including eight 4-mm histologic section for immunohistochemical study of NF-kB and BCL-10 and three 10-mm of section in eppendorf tube for RNA extraction and subsequent RT-PCR for t1118 translocation determination which will be performed at the central laboratory In addition serum from 5 mL of coagulated blood as well as peripheral blood mononuclear cells from 3 mL of heparized blood will also collected before treatment for Hp-serology and CYP 2C1819 genetic polymorphism detection respectively Hp-positive patients will receive 2-week of triple therapy consisting of omeprazole amoxicillin and clarithromycin OAC regimen and have first follow-up endoscopy 4 weeks later to determine the status of Hp infection and tumor response Patients will then have sequential follow-up endoscopic examinations every 3 months until complete histological remission CR or disease progression then every 6 months for complete responders Patients with hg-MALT lymphoma who have stable or progressive disease after Hp eradication will immediately refer for systemic chemotherapy CR was defined as regression of lymphoid infiltration to Wotherspoons score 2 on all pathological sections of endoscopic biopsy specimens The predictive value of NF-kB BCL-10 and t1118 for complete histological remission after Hp eradication will be determined
Expected Results 1st-line antibiotic therapy will achieve complete histologic remission in 70-80 of Hp-positive stage IE gastric lg-MALT lymphoma and in 50-60 of stage IE hg-MALT lymphoma The objective histologic CR rate in stage IIE-1 disease may be 30-40 for low-grade tumor and 20-30 for high-grade ones The sensitivity and specificity of NF-kB and BCL-10 positive nuclear staining by IHC and of t1118 in predicting the Hp-independence will be both 80 - 90 Ten - twenty per cent of enrolled patients will have CYP2C19 m1m1 m1m2 or m2m2 genotypes considered as omeprazole poor metabolizer and they might have higher Hp eradication rate than those extensive metabolizers
Aims A nationwide study to prospectively validate
1 The complete histological and molecular remission rate for antibiotics as 1st-line therapy for Hp-positive early-stage gastric lg- and hg-MALT lymphoma
2 The durability of complete histological remission after antibiotics
3 The usefulness of pattern of NF-kB and BCL-10 by IHC staining in prospectively predicting the Hp-dependence of gastric lg- and hg-MALT lymphoma
4 The frequency of t1118 translocation in gastric lg- and hg-MALT lymphoma in Taiwan
5 The association between the CYP2C1819 genetic polymorphisms and eradication of Hp infection after antibiotics
Materials and Methods Patients with newly histologically proven stage IE IIE-1 gastric lg- and hg-MALT lymphoma are eligible Pre-treatment Hp infection status will be determined by histology rapid urease test and serology At time of registration patients should agree to provide endoscopic biopsy specimen including eight 4-mm histologic section for immunohistochemical study of NF-kB and BCL-10 and three 10-mm of section in eppendorf tube for RNA extraction and subsequent RT-PCR for t1118 translocation determination which will be performed at the central laboratory In addition serum from 5 mL of coagulated blood as well as peripheral blood mononuclear cells from 3 mL of heparized blood will also collected before treatment for Hp-serology and CYP 2C1819 genetic polymorphism detection respectively Hp-positive patients will receive 2-week of triple therapy consisting of omeprazole amoxicillin and clarithromycin OAC regimen and have first follow-up endoscopy 4 weeks later to determine the status of Hp infection and tumor response Patients will then have sequential follow-up endoscopic examinations every 3 months until complete histological remission CR or disease progression then every 6 months for complete responders Patients with hg-MALT lymphoma who have stable or progressive disease after Hp eradication will immediately refer for systemic chemotherapy CR was defined as regression of lymphoid infiltration to Wotherspoons score 2 on all pathological sections of endoscopic biopsy specimens The predictive value of NF-kB BCL-10 and t1118 for complete histological remission after Hp eradication will be determined
Expected Results 1st-line antibiotic therapy will achieve complete histologic remission in 70-80 of Hp-positive stage IE gastric lg-MALT lymphoma and in 50-60 of stage IE hg-MALT lymphoma The objective histologic CR rate in stage IIE-1 disease may be 30-40 for low-grade tumor and 20-30 for high-grade ones The sensitivity and specificity of NF-kB and BCL-10 positive nuclear staining by IHC and of t1118 in predicting the Hp-independence will be both 80 - 90 Ten - twenty per cent of enrolled patients will have CYP2C19 m1m1 m1m2 or m2m2 genotypes considered as omeprazole poor metabolizer and they might have higher Hp eradication rate than those extensive metabolizers
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None