Gastric MALT LymphomaNCT00327132
Prospective Study of First-line Antibiotic Therapy for Early-stage Gastric MALT Lymphoma for Treatment Outcome
A study testing Omeprazole, Amoxicillin, Clarithromycin in people with Gastric MALT Lymphoma, run by National Health Research Institutes, Taiwan at 6 sites in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Gastric MALT Lymphoma
- What is being tested?
- Omeprazole, Amoxicillin, Clarithromycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 6 sitesTaiwan
- Study dates
- Jul 2006to Dec 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The patients must have histologically confirmed primary gastric MALT lymphoma with or without clustering large cells (extranodal marginal zone lymphoma, and diffuse large cell lymphoma with features of MALT by REAL/WHO classification, Harris NL et al. 1994).
- 1.1 The diagnosis of primary gastric lymphoma must fulfill the criteria of Dawson [38].
- (1)No enlargement of peripheral or mediastinal lymph node;
- (2)Peripheral blood smear revealing no leukemic or lymphomatous abnormalities;
- (3)Predominant of alimentary tract lesions with any adenopathy corresponding to accepted lymphatic drainage route; and
- (4)No involvement of liver or spleen except by extension of contiguous disease.
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- 1.2 The diagnosis of MALT lymphoma will be made by histopathologists from individual hospitals, in accordance with criteria defined by Isaacson et al. and Chang et al, and will be reviewed by the members of the TCOG Pathology Committee. This pathology review mechanism had been functioned well in the previous T1296 study (see J Natl Cancer Inst. 2005;97:1345-53)
- 1.3 The patient must have no prior chemotherapy or radiotherapy for his/her gastric lg- or hg-MALToma.
- Patients must have evaluable disease by endoscopy and/or the nodal status by computed tomography. Endoscopic ultrasonography (EUS) is mandatory to evaluate the depth of tumor infiltration and for status of perigastric lymph node enlargement.
- Patients must have documented H. pylori infection before treatment, which will be evaluated by the following tests: histology, rapid urease test (CLO-test), C-13 urease breath test and serology.
- 3.1 The following will be considered to have H. pylori infection: if any of above 4 tests show positive result.
- Patients must have either stage IE or IIE-1 disease, according to an adaptation of the Ann Abor staging system modified by Musshoff for primary extranodal lymphoma.
- 4.1 Stage IE : lymphoma confined to the gastric wall without lymph node involvement.
- 4.2 Stage IIE : localized involvement of one or more GI site(s) on one side of the diaphragm with lymph node involvement, any depth of lymphoma infiltration into the gut wall. 4.21 Stage IIE-1: involvement of perigastric lymph node. 4.22 Stage IIE-2: abdominal, but beyond perigastric, lymph nodal involvement.
- Patient must have signed the informed consent and agree to provide achieved pathologic material for immunohistochemical study and for RT-PCR t(11;18)(q21;q21) determination.
Who cannot join
- Patients with extensive gastrointestinal tract involvement are not eligible.
- Patients with previous history of extranodal lymphoma are not eligible.
- Patients with stage IIE-2 or beyond disease: infiltration of regional lymph node, e.g. paraaortic, renal hilar, retroperitoneal, mesenteric, or lymph node of gastrosplenic ligament and of hepatoduodenal ligament; or involvement of lymph node above and below diaphragm (Stage III) or other visceral organ involvement (stage IV) are not eligible.
- Patients with cardiopulmonary status that do not allow repeat endoscopy are not eligible.
- Patients with prior antibiotics, chemo- or radiotherapy for their gastric lymphoma are not eligible.
- Patients who had previous anti-H. pylori therapy and without pretreatment pathology achieve material for histological review and immunohistochemical study are not eligible.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Taiwan6 sites
Kaohsiung Medical University Hospital
Kaohsiung City, 80708
China Medical University Hospital
Taichung, 40447
Mackay Memorial Hospital
Taipei, 104
National Taiwan University Hospital
Taipei, 112
Tri-Services General Hospital
Taipei, 11490
National Taiwan University Hospital
Taipei, 115
About this study
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
- The complete histological and molecular remission rate for antibiotics as 1st-line therapy for Hp-positive early-stage gastric lg- and hg-MALT lymphoma
- The durability of complete histological remission after antibiotics
- 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
- The frequency of t(11;18) translocation in gastric lg- and hg-MALT lymphoma in Taiwan.
- The association between the CYP2C18/19 genetic polymorphisms and eradication of Hp infection after antibiotics.
Read the 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
- The complete histological and molecular remission rate for antibiotics as 1st-line therapy for Hp-positive early-stage gastric lg- and hg-MALT lymphoma
- The durability of complete histological remission after antibiotics
- 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
- The frequency of t(11;18) translocation in gastric lg- and hg-MALT lymphoma in Taiwan.
- 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 .
- Conditions
- Gastric MALT Lymphoma
- Being tested
- Omeprazole, Amoxicillin, Clarithromycin
- Keywords
- Early-stage Lg/Hg Gastric MALT Lymphoma, Eradication of Helicobacter pylori (Hp)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omeprazole, Amoxicillin, ClarithromycinDrug
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Not described Receives: Drug: Omeprazole, Amoxicillin, Clarithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hp eradication rate and complete histological rate
Measured: 10 years
Secondary outcomes (1)
overall survival (OS)Relapse-free survival (RFS)
Measured: 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2006 (estimated)
- Study startJul 2006
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric MALT LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- National Taiwan University Hospital, Tri-Service General Hospital (TSGH), Chang Gung Memorial Hospital, China Medical University Hospital, Changhua Christian Hospital, Chi Mei Medical Hospital
- Responsible party
- Sponsor
- Investigators
- Jaw-Town, Lin, M.D., PHD, Principal investigator, Taiwan cooperative oncology groupLi Tzong Chen, M.D., Ph.D., Principal investigator, Taiwan cooperative oncology group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00327132
- Sponsor's protocol ID
- T3206
- Status last verified
- Mar 2016
- First submitted
- 17 May 2006
- Last updated
- 25 Mar 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00327132
- Acronym / sponsor ID
- T3206
- Conditions
- Gastric MALT Lymphoma
- Keywords
- Early-stage Lg/Hg Gastric MALT Lymphoma, Eradication of Helicobacter pylori (Hp)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- National Taiwan University Hospital, Tri-Service General Hospital (TSGH), Chang Gung Memorial Hospital, China Medical University Hospital, Changhua Christian Hospital, Chi Mei Medical Hospital
- Study start
- Jul 2006
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 18 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- The complete histological and molecular remission rate for antibiotics as 1st-line therapy for Hp-positive early-stage gastric lg- and hg-MALT lymphoma
- The durability of complete histological remission after antibiotics
- 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
- The frequency of t(11;18) translocation in gastric lg- and hg-MALT lymphoma in Taiwan.
- 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
- The complete histological and molecular remission rate for antibiotics as 1st-line therapy for Hp-positive early-stage gastric lg- and hg-MALT lymphoma
- The durability of complete histological remission after antibiotics
- 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
- The frequency of t(11;18) translocation in gastric lg- and hg-MALT lymphoma in Taiwan.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Drug: Omeprazole, Amoxicillin, Clarithromycin |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- The patients must have histologically confirmed primary gastric MALT lymphoma with or without clustering large cells (extranodal marginal zone lymphoma, and diffuse large cell lymphoma with features of MALT by REAL/WHO classification, Harris NL et al. 1994).
- Patients must have evaluable disease by endoscopy and/or the nodal status by computed tomography. Endoscopic ultrasonography (EUS) is mandatory to evaluate the depth of tumor infiltration and for status of perigastric lymph node enlargement.
- Patients must have documented H. pylori infection before treatment, which will be evaluated by the following tests: histology, rapid urease test (CLO-test), C-13 urease breath test and serology.
- Patients must have either stage IE or IIE-1 disease, according to an adaptation of the Ann Abor staging system modified by Musshoff for primary extranodal lymphoma.
- Patient must have signed the informed consent and agree to provide achieved pathologic material for immunohistochemical study and for RT-PCR t(11;18)(q21;q21) determination.
Key exclusion criteria (6 listed)
- Patients with extensive gastrointestinal tract involvement are not eligible.
- Patients with previous history of extranodal lymphoma are not eligible.
- Patients with stage IIE-2 or beyond disease: infiltration of regional lymph node, e.g. paraaortic, renal hilar, retroperitoneal, mesenteric, or lymph node of gastrosplenic ligament and of hepatoduodenal ligament; or involvement of lymph node above and below diaphragm (Stage III) or other visceral organ involvement (stage IV) are not eligible.
- Patients with cardiopulmonary status that do not allow repeat endoscopy are not eligible.
- Patients with prior antibiotics, chemo- or radiotherapy for their gastric lymphoma are not eligible.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omeprazole, Amoxicillin, Clarithromycin | Drug | Experimental Arm |
Primary outcome
Hp eradication rate and complete histological rate
Time frame: 10 years
1 secondary outcome
overall survival (OS)Relapse-free survival (RFS)
Time frame: 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2016.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jaw-Town, Lin, M.D., PHD principal investigator
Taiwan cooperative oncology group
Li Tzong Chen, M.D., Ph.D. principal investigator
Taiwan cooperative oncology group
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Omeprazole, Amoxicillin, Clarithromycin in people with Gastric MALT Lymphoma, run by National Health Research Institutes, Taiwan at 6 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hp eradication rate and complete histological rate (time frame: 10 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2016.