Biaxin Based Antibiotic Therapy in Previously Untreated, Advanced Stage Indolent Lymphoma

Biaxin(Clarithromycin)Based Antibiotic Therapy In Previously Untreated, Advanced Stage Indolent Lymphoma

The purpose of this study is to see if a treatment with Biaxin (clarithromycin) which is an antibiotic given by mouth for 3 months can delay the growth of your lymphoma or shrink the lymphoma. We would also like to see how Biaxin (clarithromycin) works on lymphoma and blood cells.There is some evidence that this medication may change the behavior of lymphocytes, in addition to its known anti-infection activity.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: BIAXIN (CLARITHROMYCIN); Drug: Biaxin (clarithromycin)

Detailed Description

The primary objective of this study is to evaluate a biaxin (clarithromycin)-based antibiotic therapy in previously untreated patients with indolent lymphoma who do not require active lymphoma therapy (utilizing GELF criteria,). This is the primary objective Response rate (CR + PR) stratified for Follicular/Non-Follicular disease.

The secondary objectives of this study are to understand the biologic correlates of indolent lymphoma biaxin (clarithromycin) response and progression:

Response rate (CR + PR) according to H. pylori positive or negative (RR with a confidence interval will be estimated for each subset). Immunohistochemistry in all diagnostic biopsy specimens: Lymphocyte- Activated Macrophage (CD68) and other selected markers to clarify tumor infiltrating cells. Peripheral blood mononuclear cell (PBMCs) studies to evaluate possible HDAC (histone deacetylase) inhibition with biaxin (clarithromycin) therapy.

• Study Type: Observational
• Enrollment (Actual): 36

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Previously Untreated follicular lymphoma or non-follicular lymphoma will be recrited at MSKCC

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of follicular lymphoma: grades I, II, or IIIA, or non-follicular lymphoma: lymphoplasmacytoid lymphoma, small lymphocytic lymphoma, marginal B-cell lymphoma, or MALT lymphoma (as defined in the WHO classification1) as reviewed by a hematopathologist at Memorial Hospital.

• Staging fulfills criteria for no initial treatment according to GELF criteria for advanced stage disease. None of the following should be present:

  • A nodal or extranodal mass with a diameter of >7 cm,
  • Involvement of at least three nodal sites [each with a diameter of >3 cm],
  • Systemic symptoms,
  • Symptomatic splenomegaly,
  • Ureteral compression.
  • No prior treatment for lymphoma is permitted.
  • Measurable disease is required.
  • Karnofsky performance status > 70%
  • The patient may not have a previous history of radiation therapy.
  • Patient or guardian must be able to sign voluntary written consent.
  • Male or female patients 18 years of age or greater.

Exclusion Criteria:

• Allergy to biaxin (clarithromycin), erythromycin, or other macrolide antibiotic. Patients requiring use of ergot derivatives, pimozide, cisapride, or astemizole; combination with ranitidine bismuth citrate should not be used in patients with history of acute porphyria or CrCl <25 mL/minute.
• Prior treatment with Biaxin (clarithromycin) during the prior 6 months.
• Histologic diagnosis of follicular grade 3B or aggressive non-Hodgkin's lymphoma.
• Histologic evidence of transformation from low grade/indolent NHL to aggressive NHL.
• Prior treatment for non-Hodgkin's lymphoma.
• Regional lymphoma (peripheral stages I and II) eligible for involved field irradiation.

• GELF criteria21 for institution of systemic chemotherapy, which includes:

  • A nodal or extranodal mass with a diameter of >7 cm,
  • Involvement of at least three nodal sites [each with a diameter of >3 cm],
  • Systemic symptoms,
  • Symptomatic splenomegaly,
  • Ureteral compression.
• Patients with a known history of HIV, Hepatitis B or C seropositivity.
• Patients who require therapy with systemic corticosteroids.
• Prior history of malignancy within the past five years or a concurrent malignancy, with the exceptions of cutaneous basal cell carcinoma or carcinoma in situ of the uterine cervix.
• Pregnant or lactating women, since imaging cannot be done in this setting.18

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; lymphoma follicular	Drug: BIAXIN (CLARITHROMYCIN); Biaxin (clarithromycin) 500 mg will be administered by mouth twice daily for 12 weeks in all patients. In H. pylori positive patients, Prevpak standard therapy (lansoprazole, amoxicillin, clarithromycin) will be administered for the first 2 weeks.Following Biaxin (clarithromycin) antibiotic therapy, the patient will be reassessed for eradication of H. pylori if previously present.
2; lymphoma non-follicular	Drug: Biaxin (clarithromycin); Biaxin (clarithromycin) 500 mg will be administered by mouth twice daily for 12 weeks in all patients. In H. pylori positive patients, Prevpak standard therapy (lansoprazole, amoxicillin, clarithromycin) will be administered for the first 2 weeks.Following Biaxin (clarithromycin) antibiotic therapy, the patient will be reassessed for eradication of H. pylori if previously present.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective of this study is to evaluate a biaxin (clarithromycin)-based antibiotic therapy in previously untreated patients with indolent lymphoma who do not require active lymphoma therapy (utilizing GELF criteria,).	conclusion of study

Secondary Outcome Measures

Outcome Measure	Time Frame
The secondary objectives of this study are to understand the biologic correlates of indolent lymphoma biaxin (clarithromycin) response and progression	conclusion of study

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Carol Portlock, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Portlock CS, Hamlin PA, Gerecitano JF, Noy A, Palomba ML, Walkley J, Corcoran S, Migliacci J, Schoder H, Papanicolaou G, Markowitz AJ. A Positive Prospective Trial of Antibiotic Therapy in Advanced Stage, Non-Bulky Indolent Lymphoma. Tumor Microenviron Ther. 2015 Feb;2(1):14-18. doi: 10.1515/tumor-2015-0001. Epub 2015 Feb 18.

Helpful Links

• Memorial Sloan-Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: April 13, 2007
• First Submitted That Met QC Criteria: April 16, 2007
• First Posted (Estimate): April 17, 2007

Study Record Updates

• Last Update Posted (Estimate): September 18, 2014
• Last Update Submitted That Met QC Criteria: September 17, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Lymphoma; Untreated; Advanced Stage; Advanced Stage Lymphoma; Untreated Lymphoma; 07-038
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Clarithromycin
• Other Study ID Numbers: 07-038