A Phase II Study of Doxycycline in Relapsed NHL

University of Rochester

Status and phase

Terminated

Phase 2

Conditions

T-Cell Lymphoma

Waldenstrom Macroglobulinemia

Lymphoma, Follicular

Malignant Lymphoma - Lymphoplasmacytic

Adult Diffuse Large B-Cell Lymphoma

Small Lymphocytic Lymphoma

Chronic Lymphocytic Leukemia (CLL)

Mantle Cell Lymphoma Recurrent

Marginal Zone B-Cell Lymphoma

Treatments

Drug: Doxycycline

Study type

Interventional

Funder types

Other

Identifiers

NCT02086591

50370

120145

Details and patient eligibility

About

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

Full 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.

Enrollment

7 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.