Helicobacter – Lymphoma – Radiation Part I: Eradication, Part II: Radiation

Condition(s) targeted: Lymphoma; Lymphoma, Non-Hodgkin

Intervention: proton pump inhibitor (Drug); clarithromycin (Drug); amoxicillin (Drug); metronidazole (Drug); radiation therapy (Procedure)

Phase: Phase 3

Status: Recruiting

Sponsored by: Dresden University of Technology

Official(s) and/or principal investigator(s):
Andrea Morgner-Miehlke, MD, PhD, Principal Investigator, Affiliation: Med. Dept. I, University Hospital, Technical University Dresden

Overall contact:
Andrea Morgner-Miehlke, MD, PhD, Phone: +49351458, Ext: 2986, Email: andrea.morgner-miehlke@uniklinikum-dresden.de

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.

Official title: Treatment of Low-Grade Gastric Non-Hodgkin‘s Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT) Type Stages IE & II1E (HELYX-Study)

Study design: Treatment, Randomized, Open Label, Dose Comparison, Single Group Assignment, Efficacy Study

Primary outcome:

remission status after eradication therapy 3-monthly

continuous complete remission (CCR) during follow-up

remission status after radiation therapy (36 Gy vs 25.2 Gy)

continuous complete remission after radiation therapy during follow-up

Secondary outcome:

endoscopic controls every 3 months during the first year

endoscopic controls twice yearly in the second year after CR

complete tumor staging once yearly

relapse after therapy after each intervention

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.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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

Andrea Morgner-Miehlke, MD, PhD, Phone: +49351458, Ext: 2986, Email: andrea.morgner-miehlke@uniklinikum-dresden.de

Institute for Pathology, Bayreuth, Bavaria 95445, Germany; Recruiting
Manfred Stolte, MD, PhD, Phone: +49921400, Ext: 5600, Email: pathologie.klinikum@bnbt.de
Michael Vieth, MD, PhD, Phone: +49921400, Ext: 5602, Email: Vieth.LKPathol@uni-bayreuth.de
Michael Vieth, MD, PhD, Sub-Investigator

Med. Dept. I, Gastroenterology, Dresden, Saxonia 01307, Germany; Recruiting
Gerhard Ehninger, MD, PhD, Phone: +49251458, Ext: 4190, Email: gerhard.ehninger@uniklinikum-dresden.de
Stephan Miehlke, MD, PhD, Phone: +49351458, Ext: 5645, Email: stephan.miehlke@uniklinikum-dresden.de
Stephan Miehlke, MD, PhD, Sub-Investigator

Dept. for Radiation Therapy & Radiooncology, University Hospital, Germany, Saxonia 01307, Germany; Recruiting
Thomas Herrmann, MD, PhD, Phone: +49351458, Ext: 3373, Email: thomas.herrmann@uniklinikum-dresden.de
Monique Dawel, MD, Phone: +49351458, Ext: 3373, Email: monique.dawel@uniklinikum-dresden.de
Monique Dawel, MD, Sub-Investigator

Related publications:

Akagi T, Motegi M, Tamura A, Suzuki R, Hosokawa Y, Suzuki H, Ota H, Nakamura S, Morishima Y, Taniwaki M, Seto M. A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue. Oncogene. 1999 Oct 14;18(42):5785-94.

Alpen B, Neubauer A, Dierlamm J, Marynen P, Thiede C, Bayerdorfer E, Stolte M. Translocation t(11;18) absent in early gastric marginal zone B-cell lymphoma of MALT type responding to eradication of Helicobacter pylori infection. Blood. 2000 Jun 15;95(12):4014-5. No abstract available.

Bayerdorffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group. Lancet. 1995 Jun 24;345(8965):1591-4.

Hussell T, Isaacson PG, Crabtree JE, Spencer J. The response of cells from low-grade B-cell gastric lymphomas of mucosa-associated lymphoid tissue to Helicobacter pylori. Lancet. 1993 Sep 4;342(8871):571-4.

Liu H, Ruskon-Fourmestraux A, Lavergne-Slove A, Ye H, Molina T, Bouhnik Y, Hamoudi RA, Diss TC, Dogan A, Megraud F, Rambaud JC, Du MQ, Isaacson PG. Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy. Lancet. 2001 Jan 6;357(9249):39-40.

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.

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.

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. Review.

Ruskone-Fourmestraux A, Dragosics B, Morgner A, Wotherspoon A, Dd Jong D. Paris staging system for primary gastrointestinal lymphomas. Gut. 2003 Jun;52(6):912-3. No abstract available.

Starting date: November 2001
Ending date: October 2013
Last updated: March 23, 2007