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

NCT ID: NCT00154440

Last Updated: 2007-03-26

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-11-30
• Study Completion Date: 2013-10-31

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.

Conditions

Lymphoma; Lymphoma, Non-Hodgkin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

proton pump inhibitor

Intervention Type: DRUG

clarithromycin

Intervention Type: DRUG

amoxicillin

Intervention Type: DRUG

metronidazole

Intervention Type: DRUG

radiation therapy

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Technische Universität Dresden

OTHER

Sponsor Role: lead

Principal Investigators

Andrea Morgner-Miehlke, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Institute for Pathology

Bayreuth, Bavaria, Germany

Site Status: RECRUITING

Med. Dept. I, Gastroenterology

Dresden, Saxony, Germany

Site Status: RECRUITING

Dept. for Radiation Therapy & Radiooncology, University Hospital

Germany, Saxony, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Andrea Morgner-Miehlke, MD, PhD

Role: CONTACT

andrea.morgner-miehlke@uniklinikum-dresden.de

+49351458 ext. 2986

Renate Schmelz, MD

Role: CONTACT

renate.schmelz@uniklinikum-dresden.de

+49351458 ext. 4702/2986

Facility Contacts

Manfred Stolte, MD, PhD

Role: primary

pathologie.klinikum@bnbt.de

+49921400 ext. 5600

Michael Vieth, MD, PhD

Role: backup

Vieth.LKPathol@uni-bayreuth.de

+49921400 ext. 5602

Gerhard Ehninger, MD, PhD

Role: primary

gerhard.ehninger@uniklinikum-dresden.de

+49251458 ext. 4190

Stephan Miehlke, MD, PhD

Role: backup

stephan.miehlke@uniklinikum-dresden.de

+49351458 ext. 5645

Thomas Herrmann, MD, PhD

Role: primary

thomas.herrmann@uniklinikum-dresden.de

+49351458 ext. 3373

Monique Dawel, MD

Role: backup

monique.dawel@uniklinikum-dresden.de

+49351458 ext. 3373

References

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. doi: 10.1038/sj.onc.1203018.

Reference Type: BACKGROUND

PMID: 10523859 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10939796 (View on PubMed)

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. doi: 10.1016/s0140-6736(95)90113-2.

Reference Type: BACKGROUND

PMID: 7783535 (View on PubMed)

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. doi: 10.1016/0140-6736(93)91408-e.

Reference Type: BACKGROUND

PMID: 8102718 (View on PubMed)

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. doi: 10.1016/S0140-6736(00)03571-6.

Reference Type: BACKGROUND

PMID: 11197361 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9308704 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9586910 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9394762 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12740354 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30327875 (View on PubMed)

Other Identifiers

HELYX Study

Identifier Type: -

Identifier Source: org_study_id