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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00154440
• Other study ID #: HELYX Study
• Status: Recruiting
• Phase: Phase 3
• First received: September 8, 2005
• Last updated: March 23, 2007
• Start date: November 2001
• Est. completion date: October 2013

Study information

• Verified date: March 2007
• Source: Technische Universität Dresden
• Contact: Andrea Morgner-Miehlke, MD, PhD
• Phone: +49351458
• Email: andrea.morgner-miehlke[@]uniklinikum-dresden.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• proton pump inhibitor

• clarithromycin

• amoxicillin

• metronidazole

Procedure:
• radiation therapy

Locations

Country	Name	City	State
Germany	Institute for Pathology	Bayreuth	Bavaria
Germany	Med. Dept. I, Gastroenterology	Dresden	Saxonia
Germany	Dept. for Radiation Therapy & Radiooncology, University Hospital	Germany	Saxonia

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität Dresden

Country where clinical trial is conducted

Germany, 

References & Publications (9)

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. — View Citation

Alpen B, Neubauer A, Dierlamm J, Marynen P, Thiede C, Bayerdörfer 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. — View Citation

Bayerdörffer 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. — View Citation

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. — View Citation

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. — View Citation

Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wündisch T, Ehninger G, Stolte M, Bayerdörffer 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. — View Citation

Ruskoné-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. — View 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. — View Citation

Thiede C, Morgner A, Alpen B, Wündisch T, Herrmann J, Ritter M, Ehninger G, Stolte M, Bayerdörffer 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	remission status after eradication therapy 3-monthly
Primary	continuous complete remission (CCR) during follow-up
Primary	remission status after radiation therapy (36 Gy vs 25.2 Gy)
Primary	continuous complete remission after radiation therapy during follow-up
Secondary	endoscopic controls every 3 months during the first year
Secondary	endoscopic controls twice yearly in the second year after CR
Secondary	complete tumor staging once yearly
Secondary	relapse after therapy after each intervention