A Phase II Study of Doxycycline in Relapsed NHL

October 27, 2016 updated by: Carla Casulo, University of Rochester
The purpose of this study is to determine whether doxycycline is effective in the treatment of relapsed Non Hodgkin Lymphomas (NHL).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

7

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Doxycycline
Doxycycline 200 mg twice daily
Drug: Doxycycline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: Three months

Overall response rate is defined as the percentage of patients with disease progression. Progression is defined as:

  • Appearance of a new lesion on fluorodeoxyglucose (FDG)-positron emission tomography or computerized tomography
  • ≥50% increase in sum of the product of the node dimensions (SPD) of more than one node or in greatest diameter of any previously identified node >1 cm in its short axis from nadir.
  • To be considered progressive disease, a lymph node with a diameter of the short axis of less than 1.0 cm must increase by 50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis.
  • At least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis.
Three months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Patients With Progression Free Survival
Time Frame: One year
Progression free survival is defined as the percentage of patients with stable disease or no death. Stable disease is defined as less than a partial response but is not progressive disease. Partial Response (PR)-At least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses as determined byFDG-PET for CT scan. No increase should be observed in the size of other nodes, liver, or spleen. Patients who achieve a CR by the above criteria, but who have persistent morphologic bone marrow involvement will be considered partial responders. When the bone marrow was involved before therapy and a clinical CR was achieved, but with no bone marrow assessment after treatment, patients should be considered partial responders.
One year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Exploratory Objective
Time Frame: One year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Rochester

Investigators

  • Principal Investigator: Carla Casulo, MD, University of Rochester

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

July 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

February 26, 2014

First Submitted That Met QC Criteria

March 11, 2014

First Posted (Estimate)

March 13, 2014

Study Record Updates

Last Update Posted (Estimate)

December 22, 2016

Last Update Submitted That Met QC Criteria

October 27, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 50370
  • 120145 (IND)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Lymphoma, Follicular

Clinical Trials on Doxycycline

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Georgia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe