Clinical trial NCT00154440: Helicobacter - Lymphoma - Radiation Part I: Eradication, Part II: Radiation
Official title: Treatment of Low-Grade Gastric Non-Hodgkin's Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT) Type Stages IE & II1E (HELYX-Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lymphoma
Lymphoma, Non-Hodgkin
Keywords: primary gastric MALT lymphoma
Helicobacter pylori
eradication therapy
radiation
marginal zone B-cell lymphoma
Mucosa-associated Lymphoid Tissue
B-cell Non-Hodgkin's Lymphoma of the stomach
primary gastric lymphoma
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
First posted: 2005-09-12
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The first objective of this study is to confirm the results of complete remission of low-grade gastric MALT lymphoma stage IE \& II1E after H. pylori eradication on a larger number of patients (HELYX Part I). If there is no response to the antibiotic therapy, the role of radiotherapy on the course of gastric MALT lymphoma will be investigated as a consecutive therapeutic option for patients that are H. pylori- negative, t(11;18)-positive or failure candidates after eradication therapy. Furthermore, the method of radiation, and the radiation dose will be investigated and standardized. HELYX PART II is therefore a randomized equivalent study comparing the standard dose of 36Gy vs. a reduced dose of 25.2Gy locoregional. Additional molecular genetic analysis will be performed to try to understand pathogenetic mechanisms of lymphomagenesis.

Detailed description: Experimental data have extended the knowledge of the mere association of gastric MALT lymphoma and infection with Helicobacter pylori. If we summarise the reports to date on the results of treatment of gastric low-grade MALT lymphoma in an early clinical stage (EI) by H. pylori eradication we find a complete remission figure of 77% in more than 200 patients.

As a therapy with less side effects than radiation, surgery or chemotherapy and as a stomach-conserving treatment, eradication of H. pylori in patients with low-grade gastric MALT lymphoma in stages IE \& II1E should be the treatment of the choice within clinical trials since there are no long-term results available thus far. Besides, pretreatment patient selection and careful follow-up with endoscopy, biopsies and clinical staging including endoscopic ultrasonography is necessary. However, a five to ten year-follow-up will be necessary before the definitive value of Helicobacter pylori eradication can be established. Furthermore, since not all patients respond to this therapy research into the pathogenetic mechanisms of lymphomagenesis is inevitable.

Approximately 20% of patients with antigen-positive, primary gastric low-grade MALT lymphoma in stage I will not respond to eradication therapy. Hence, a consecutive salvage therapy other than surgery is much needed. The aim of the second part of this study is to establish radiation therapy as a salvage therapy. Furthermore, the effect of a reduced radiation dose (25.2Gy) compared to the standard dose (36Gy) will be investigated with the aim of non-inferiority of both doses.

Eligibility criteria: Inclusion Criteria:

* histologically diagnosed, primary gastric low-grade B-cell MALT lymphoma stages IE or II1E, Helicobacter pylori-positive (in histology, urease test , and serology) for inclusion into HELYX part I
* histologically diagnosed, primary gastric low-grade B-cell MALT lymphoma stages IE or II1E, Helicobacter pylori-negative (in histology, urease test, and serology) for inclusion into HELYX part II
* patients who achieved a study end point of HELYX I: partial remission or no change 12 months after successful antibiotic therapy for inclusion into HELYX part II,
* age \> 18 and \< 75 years
* Karnofsky-Index \> 60%
* sufficient liver function, defined as bilirubin \< 34µmol/l
* sufficient renal function, defined as creatinine \< 133µmol/l
* written informed consent
* complete clinical tumor staging

Exclusion Criteria:

* primary gastric low-grade MALT lymphoma, stages \>II1E or gastric high-grade lymphoma or other lymphoma entities of the stomach e.g. lymphoblastic lymphoma or Burkitt's lymphoma
* age \< 18 and \> 75 years
* Karnofsky-Index \< 60%
* insufficient liver and renal function (see above)
* HIV-infection
* pregnancy or nursing

Primary outcomes:
measure: remission status after eradication therapy 3-monthly
measure: continuous complete remission (CCR) during follow-up
measure: remission status after radiation therapy (36 Gy vs 25.2 Gy)
measure: continuous complete remission after radiation therapy during follow-up
Secondary outcomes:
measure: endoscopic controls every 3 months during the first year
measure: endoscopic controls twice yearly in the second year after CR
measure: complete tumor staging once yearly
measure: relapse after therapy after each intervention
Other outcomes:
Locations:
city: Bayreuth
country: Germany
facility: Institute for Pathology
state: Bavaria
city: Dresden
country: Germany
facility: Med. Dept. I, Gastroenterology
state: Saxonia
city: Germany
country: Germany
facility: Dept. for Radiation Therapy & Radiooncology, University Hospital
state: Saxonia
Study officials:
affiliation: Med. Dept. I, University Hospital, Technical University Dresden
name: Andrea Morgner-Miehlke, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wundisch T, Ehninger G, Stolte M, Bayerdorffer E. Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst. 1997 Sep 17;89(18):1350-5. doi: 10.1093/jnci/89.18.1350.
citation: Schechter NR, Portlock CS, Yahalom J. Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone. J Clin Oncol. 1998 May;16(5):1916-21. doi: 10.1200/JCO.1998.16.5.1916.
citation: Thiede C, Morgner A, Alpen B, Wundisch T, Herrmann J, Ritter M, Ehninger G, Stolte M, Bayerdorffer E, Neubauer A. What role does Helicobacter pylori eradication play in gastric MALT and gastric MALT lymphoma? Gastroenterology. 1997 Dec;113(6 Suppl):S61-4. doi: 10.1016/s0016-5085(97)80014-5.
citation: Ruskone-Fourmestraux A, Dragosics B, Morgner A, Wotherspoon A, De Jong D. Paris staging system for primary gastrointestinal lymphomas. Gut. 2003 Jun;52(6):912-3. doi: 10.1136/gut.52.6.912. No abstract available.
citation: Schmelz R, Miehlke S, Thiede C, Brueckner S, Dawel M, Kuhn M, Ruskone-Formestraux A, Stolte M, Jentsch C, Hampe J, Morgner A. Sequential H. pylori eradication and radiation therapy with reduced dose compared to standard dose for gastric MALT lymphoma stages IE & II1E: a prospective randomized trial. J Gastroenterol. 2019 May;54(5):388-395. doi: 10.1007/s00535-018-1517-4. Epub 2018 Oct 16.