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2025-12-24 @ 9:56 PM
Ignite Modification Date:
2025-12-25 @ 7:34 PM
Study NCT ID:
NCT00327132
Status:
COMPLETED
Last Update Posted:
2016-03-25
First Post:
2006-05-17
Is NOT Gene Therapy:
False
Has Adverse Events:
False
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:
Study Overview
Official Title:
Multicentre,Prospective 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 t(11;18) translocation in gastric lg- and hg-MALT lymphoma in Taiwan.
5. The association between the CYP2C18/19 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 t(11;18) translocation in gastric lg- and hg-MALT lymphoma in Taiwan.
5. The association between the CYP2C18/19 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 t(11;18) 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 CYP2C18/19 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 t(11;18) translocation in gastric lg- and hg-MALT lymphoma in Taiwan.
5. The association between the CYP2C18/19 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 t(11;18) 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 2C18/19 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 Wotherspoon's score \<2 on all pathological sections of endoscopic biopsy specimens. The predictive value of NF-kB, BCL-10 and t(11;18) 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 t(11;18) in predicting the Hp-independence will be both 80 - 90%. Ten - twenty per cent of enrolled patients will have CYP2C19 m1/m1, m1/m2 or m2/m2 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 t(11;18) translocation in gastric lg- and hg-MALT lymphoma in Taiwan.
5. The association between the CYP2C18/19 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 t(11;18) 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 2C18/19 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 Wotherspoon's score \<2 on all pathological sections of endoscopic biopsy specimens. The predictive value of NF-kB, BCL-10 and t(11;18) 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 t(11;18) in predicting the Hp-independence will be both 80 - 90%. Ten - twenty per cent of enrolled patients will have CYP2C19 m1/m1, m1/m2 or m2/m2 genotypes (considered as omeprazole poor metabolizer), and they might have higher Hp eradication rate than those extensive metabolizers .
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: