Phase II Trial of First-line Doxycycline for Ocular Adnexal Marginal Zone Lymphoma Treatment

International Prospective Phase 2 Trial Addressing the Efficacy of First-line Chlamydophila Psittaci-eradicating Therapy With Protracted Administration of Doxycycline Followed by Eradication Monitoring and Antibiotic Re-treatment at Infection Re-occurrence in Patients With Newly Diagnosed Ocular Adnexal Marginal Zone Lymphoma (OAMZL)

Objective of this trial is to establish the efficacy of an upfront targeted therapy consisting of Chlamydophila psittaci (Cp)-eradicating therapy with prolonged administration of doxycycline followed by eradication monitoring and antibiotic re-treatment at infection re-occurrence in patients with newly diagnosed ocular adnexae marginal zone lymphoma The primary endpoint is the 2-year progression-free survival (PFS) of patients with newly diagnosed stage-IE lymphoma treated with the experimental strategy.

Study Overview

• Status: Active, not recruiting
• Conditions: Marginal Zone Lymphoma of Ocular Adnexal
• Intervention / Treatment: Drug: Doxycycline

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Messina, Italy
    • AO Ospedali Riuniti Papardo Piemonte
  • Milan, Italy
    • Ospedale San Raffaele
  • Parma, Italy
    • Ematologia
  • Piacenza, Italy
    • Ospedale Civile
  • Rome, Italy
    • Università La Sapienza
  • Torino, Italy
    • Molinette 1
  • Venezia, Italy
    • Ospedale dell'Angelo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histological diagnosis of marginal zone lymphoma of the ocular adnexae (OAMZL)
2. Single or bilateral lesion (stage IE) localised to the ocular adnexae (conjunctiva, lachrymal gland or sac, orbit soft tissue, eyelid)
3. Absence of B symptoms
4. Previously untreated patients
5. No systemic antibiotic therapy in the last three months before enrolment
6. Age >18 years
7. ECOG PS 0-2
8. Negative HIV, HBV and HCV serology
9. Adequate bone marrow, renal, and hepatic function
10. No previous or concurrent malignancies with the exception of surgically cured carcinoma in situ of the cervix, carcinoma of the skin or other cancers without evidence of disease at least from 5 years
11. Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
12. Sexually active patients of childbearing potential must implement adequate contraceptive measures during study participation
13. No concurrent treatment with other experimental drugs
14. Patient-signed informed consent obtained before registration

Exclusion Criteria:

1. Pregnant or lactating women
2. Known allergy to tetracycline
3. Patients unwilling to comply with the requirements of follow-up
4. Myasthenia gravis (tetracycline can exacerbate muscle weakness)
5. Systemic lupus erythematous (tetracycline can exacerbate this condition)
6. Patients with large or rapidly enlarging tumors requiring immediate radiotherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Doxycycline

Drug: Doxycycline; All enrolled patients will be treated with doxycycline 100 mg bid daily, orally, for four weeks followed by four weeks rest, repeated for three cycles. Response will be assessed by MRI (magnetic resonance imaging) and ophthalmologic examination at the end of the planned treatment. Patients who will achieve complete response, partial response or have a stable disease at 3 months from upfront doxycycline will be monitored for infection re-occurrence and assessed for response with MRI and ophthalmologist evaluation every six months for the first five years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression-free survival (PFS)	from the date of the start of treatment to relapse, progression or death, or to the last date of follow-up	2-year from start of treatment

Collaborators and Investigators

• Sponsor: International Extranodal Lymphoma Study Group (IELSG)
• Investigators: Study Chair: Andrés Ferreri, MD, Ospedale San Raffaele, Milan, Italy

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): May 1, 2016
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: March 26, 2013
• First Submitted That Met QC Criteria: March 26, 2013
• First Posted (Estimate): March 29, 2013

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 17, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, B-Cell, Marginal Zone; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: IELSG39