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| ID | Type | Description | Link |
|---|---|---|---|
| 120145 | Other Identifier | IND |
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Lack of accrual
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The purpose of this study is to determine whether doxycycline is effective in the treatment of relapsed Non Hodgkin Lymphomas (NHL).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Doxycycline | Experimental | Doxycycline 200 mg twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Doxycycline | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Response Rate | Overall response rate is defined as the percentage of patients with disease progression. Progression is defined as:
| Three months |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients With Progression Free Survival | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Inclusion Criteria:
Relapsed aggressive or indolent NHL following any prior treatment of the following etiologies:
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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Carla Casulo, MD | University of Rochester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Rochester | Rochester | New York | 14642 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Doxycycline | Doxycycline 200 mg twice daily Doxycycline |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| One year |
| One year |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Doxycycline | Doxycycline 200 mg twice daily Doxycycline |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||||
| Gender | Count of Participants | Participants |
| ||||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Response Rate | Overall response rate is defined as the percentage of patients with disease progression. Progression is defined as:
| Posted | Number | percentage of participants | Three months |
|
|
| |||||||||||||||||||||||||||
| Secondary | Percentage of Patients With Progression Free Survival | 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. | Data was collected on all patients who were enrolled. | Posted | Number | percentage of participants | One year |
|
| |||||||||||||||||||||||||||
| Other Pre-specified | 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. | No data displayed because Outcome Measure has zero total participants analyzed | Posted | One year |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Doxycycline | Doxycycline 200 mg twice daily Doxycycline | 0 | 7 | 6 | 7 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Photosensitivity | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| musculoskeletal and connective tissue disorder | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| alanine aminotransferase increase | Investigations | Systematic Assessment |
| ||
| creatinine increased | Investigations | Systematic Assessment |
| ||
| sepsis | Infections and infestations | Systematic Assessment |
| ||
| vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| fatigue | General disorders | Systematic Assessment |
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| face edema | General disorders | Systematic Assessment |
| ||
| pain | General disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Carla Casulo | University of Rochester | 585-273-3258 | carla_casulo@urmc.rochester.edu |
| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D008224 | Lymphoma, Follicular |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D008258 | Waldenstrom Macroglobulinemia |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006474 | Hemorrhagic Disorders |
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D004318 | Doxycycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
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