Brief Title
A Phase II Study of Doxycycline in Relapsed NHL
Official Title
A Phase II Study of Doxycycline in Relapsed NHL
Brief Summary
The purpose of this study is to determine whether doxycycline is effective in the treatment of relapsed Non Hodgkin Lymphomas (NHL).
Detailed Description
The long-term objective of this proposal is to develop more effective and less toxic therapeutic approaches for relapsed and refractory Non Hodgkin Lymphomas (NHL). Given the incurability of indolent lymphomas, innovative strategies for treatment are needed. For aggressive lymphomas such as Diffuse Large B Cell Lymphoma (DLBCL), novel treatments are particularly relevant since one third of patients have disease that will relapse or is refractory to standard therapy. Outcomes for this remaining group of patients are very poor. To address this unmet need, we have identified the antimicrobial agent doxycycline as a novel drug repurposed for lymphoma treatment based on results from a small molecule screen against Diffuse Large B Cell Lymphoma (DLBCL). Through preclinical work in his laboratory, my basic science collaborator Dr. Jiyong Zhao has found that doxycycline inhibits proliferation and survival in both activated B cell (ABC) type and germinal center B (GCB) type Diffuse Large B Cell Lymphoma (DLBCL) cell lines, as well as in Burkitt lymphoma (BL) and follicular lymphoma (FL) cell lines. Based on this preliminary data, we propose an open label, single center phase II study of doxycycline in patients with relapsed Non Hodgkin Lymphomas (NHL). We have selected a dose and schedule (200 mg BID by mouth daily) based on maximum antimicrobial dose use, and acceptance of tolerability in several studies. The planned correlative studies should help to identify potential biomarkers for response to doxycycline, such as plasma matrix metalloproteinase 9 (MMP9), and provide further insight into potential mechanisms of doxycyline action hypothesized from results of prior laboratory studies.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall Response Rate
Secondary Outcome
Percentage of Patients With Progression Free Survival
Condition
Adult Diffuse Large B-Cell Lymphoma
Intervention
Doxycycline
Study Arms / Comparison Groups
Doxycycline
Description: Doxycycline 200 mg twice daily
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
7
Start Date
March 2014
Completion Date
November 2015
Primary Completion Date
July 2015
Eligibility Criteria
Inclusion Criteria: - Relapsed aggressive or indolent NHL following any prior treatment of the following etiologies: - Diffuse large B cell lymphoma (DLBCL) - Mantle cell lymphoma (MCL) - Follicular lymphoma (FL) - Marginal zone lymphoma (MZL) - Lymphoplasmacytic lymphoma (LPL) - Waldenstrom's macroglobulinemia (WM) - Small lymphocytic lymphoma (SLL) - Chronic lymphocytic leukemia (CLL) - T cell lymphoma (TCL) - Ages ≥ 18 - Karnofsky Performance Status (KPS) ≥ 60% or Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2 - Life expectancy of at least 3 months - Measurable disease in at least one target lesion, assessable by radiographic examination with Fludeoxyglucose-Positron Emission Tomography (FDG-PET) or computed tomography (CT), bone marrow evaluation showing involvement, or peripheral blood showing involvement of lymphoma - Adequate organ function: - Absolute neutrophil count (ANC) > 500 cells/mL and platelet count > 50,000 cells/mL unless felt to be secondary to lymphoma at which any count is permissible. - Adequate renal function as determined by Creatinine (Cr) < 1.5x upper limit of normal (ULN) or estimated creatinine clearance of ≥ 60mL/min - Adequate hepatic function as determined by total bilirubin < 1.5x upper limit of normal (ULN) (unless known Gilbert syndrome), alanine aminotransferase (ALT)and aspartate aminotransferase (AST) < 2.5x upper limit of normal (ULN) Exclusion Criteria: - Known sensitivity or allergy to tetracyclines - Lack of measurable disease by computed tomography (CT) or Fludeoxyglucose-Positron Emission Tomography (FDG-PET) - Karnofsky Performance Status (KPS) <60% or Eastern Cooperative Oncology Group Performance Status (ECOG PS) >2 - Curative treatment is indicated or possible - Inadequate organ function as measured by not fulfilling above criteria - Pregnancy, positive serum human chorionic gonadotropin (hCG) within 28 days of enrollment, or breast-feeding.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Carla Casulo, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02086591
Organization ID
50370
Secondary IDs
120145
Responsible Party
Principal Investigator
Study Sponsor
University of Rochester
Study Sponsor
Carla Casulo, MD, Principal Investigator, University of Rochester
Verification Date
October 2016