A Phase II Study of Doxycycline in Relapsed NHL

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 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

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