Helicobacter – Lymphoma – Radiation Part I: Eradication, Part II: Radiation - Full Text View

Sponsor:	Dresden University of Technology
Information provided by:	Dresden University of Technology
ClinicalTrials.gov Identifier:	NCT00154440

Purpose

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.

Condition	Intervention	Phase
Lymphoma Lymphoma, Non-Hodgkin	Drug: proton pump inhibitor Drug: clarithromycin Drug: amoxicillin Drug: metronidazole Procedure: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Single Group Assignment, Efficacy Study
Official Title:	Treatment of Low-Grade Gastric Non-Hodgkin‘s Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT) Type Stages IE & II1E (HELYX-Study)

Resource links provided by NLM:

MedlinePlus related topics: Lymphoma

Drug Information available for: Amoxicillin Amoxicillin sodium Amoxicillin trihydrate Metronidazole hydrochloride Metronidazole phosphate Clarithromycin Metronidazole

U.S. FDA Resources

Further study details as provided by Dresden University of Technology:

Primary Outcome Measures:

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 Measures:

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

Estimated Enrollment:	200
Study Start Date:	November 2001
Estimated Study Completion Date:	October 2013

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

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00154440

Contacts

Contact: Andrea Morgner-Miehlke, MD, PhD	+49351458 ext 2986	andrea.morgner-miehlke@uniklinikum-dresden.de
Contact: Renate Schmelz, MD	+49351458 ext 4702/2986	renate.schmelz@uniklinikum-dresden.de

Locations

Germany, Bavaria
Institute for Pathology	Recruiting
Bayreuth, Bavaria, Germany, 95445
Contact: Manfred Stolte, MD, PhD +49921400 ext 5600 pathologie.klinikum@bnbt.de
Contact: Michael Vieth, MD, PhD +49921400 ext 5602 Vieth.LKPathol@uni-bayreuth.de
Sub-Investigator: Michael Vieth, MD, PhD
Germany, Saxonia
Med. Dept. I, Gastroenterology	Recruiting
Dresden, Saxonia, Germany, 01307
Contact: Gerhard Ehninger, MD, PhD +49251458 ext 4190 gerhard.ehninger@uniklinikum-dresden.de
Contact: Stephan Miehlke, MD, PhD +49351458 ext 5645 stephan.miehlke@uniklinikum-dresden.de
Sub-Investigator: Stephan Miehlke, MD, PhD
Dept. for Radiation Therapy & Radiooncology, University Hospital	Recruiting
Germany, Saxonia, Germany, 01307
Contact: Thomas Herrmann, MD, PhD +49351458 ext 3373 thomas.herrmann@uniklinikum-dresden.de
Contact: Monique Dawel, MD +49351458 ext 3373 monique.dawel@uniklinikum-dresden.de
Sub-Investigator: Monique Dawel, MD

Sponsors and Collaborators

Dresden University of Technology

Investigators

Principal Investigator:

Andrea Morgner-Miehlke, MD, PhD

Med. Dept. I, University Hospital, Technical University Dresden

More Information

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.

Study ID Numbers:	HELYX Study
Study First Received:	September 8, 2005
Last Updated:	March 23, 2007
ClinicalTrials.gov Identifier:	NCT00154440 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Dresden University of Technology:

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

Additional relevant MeSH terms:

Metronidazole
Anti-Infective Agents
Antiprotozoal Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Lymphoma, B-Cell, Marginal Zone
Lymphoma, B-Cell
Clarithromycin
Anti-Bacterial Agents
Antiparasitic Agents
Proton Pump Inhibitors
Therapeutic Uses
Lymphoma

Amoxicillin
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Enzyme Inhibitors
Pharmacologic Actions
Lymphatic Diseases
Protein Synthesis Inhibitors
Neoplasms
Radiation-Sensitizing Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on February 08, 2010