A Phase II Study of Doxycycline in Relapsed NHL

Small Lymphocytic Lymphoma Clinical Trial

Official title:

A Phase II Study of Doxycycline in Relapsed NHL

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02086591
• Other study ID #: 50370
• Secondary ID: 120145
• Status: Recruiting
• Phase: Phase 2
• First received: February 26, 2014
• Last updated: July 23, 2015
• Start date: March 2014
• Est. completion date: March 2018

Study information

• Verified date: July 2015
• Source: University of Rochester
• Contact: Carla Casulo, MD
• Phone: 585-273-3258
• Email: Carla_Casulo[@]urmc.rochester.edu
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether doxycycline is effective in the treatment of relapsed Non Hodgkin Lymphomas (NHL).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: March 2018
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Adult Diffuse Large B-Cell Lymphoma
• Chronic Lymphocytic Leukemia (CLL)
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Lymphoma, T-Cell
• Malignant Lymphoma - Lymphoplasmacytic
• Mantle Cell Lymphoma Recurrent
• Marginal Zone B-Cell Lymphoma
• Small Lymphocytic Lymphoma
• T-Cell Lymphoma
• Waldenstrom Macroglobulinemia

Intervention

Drug:
• Doxycycline

Locations

Country	Name	City	State
United States	University of Rochester	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
University of Rochester

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory objective	To investigate change in plasma matrix metalloproteinase 9 (MMP9) levels as a biomarker of treatment response; to assess plasma matrix metalloproteinase 9 (MMP9) expression by immunohistochemistry (IHC) and correlate to response in order to test the hypothesis that elevated intratumoral levels of plasma matrix metalloproteinase 9 (MMP9) can predict response to doxycycline. To assess activation/expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kb) and Signal transducer and activator of transcription 3 (STAT 3) pathways in archived tumor by immunohistochemistry (IHC) to predict response or resistance to doxycycline.	One year	No
Primary	Overall response rate	The aim of this study is to evaluate the efficacy of doxycycline in relapsed Non Hodgkin Lymphomas (NHL). The primary objective is to determine the overall response rate of doxycycline monotherapy in patients with relapsed indolent and aggressive Non Hodgkin Lymphomas (NHL).	Three months	No
Secondary	Progression free survival	The secondary objectives are to determine progression free survival (PFS) in all patients at one year; to determine overall survival (OS) of patients at one year; and to determine duration of response in all patients.	One year	No