Adult Diffuse Large B-Cell LymphomaPhase 2NCT02086591
A Phase II Study of Doxycycline in Relapsed NHL
A Phase 2 study testing Doxycycline in people with Adult Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma Recurrent, run by University of Rochester at 1 site in United States.
Trial summary
The purpose of this study is to determine whether doxycycline is effective in the treatment of relapsed Non Hodgkin Lymphomas (NHL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma Recurrent, Lymphoma, Follicular
- What is being tested?
- Doxycycline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2014to Nov 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 18Show fewer
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether doxycycline is effective in the treatment of relapsed Non Hodgkin Lymphomas (NHL).
Read the 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.
- Conditions
- Adult Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma Recurrent, Lymphoma, Follicular, Marginal Zone B-Cell Lymphoma, Malignant Lymphoma - Lymphoplasmacytic, Waldenstrom Macroglobulinemia
- Being tested
- Doxycycline
- Keywords
- Non Hodgkin Lymphoma, Doxycycline
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, T-Cell, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
| Study group | Role | What they receive |
|---|---|---|
| Doxycycline | Experimental | Doxycycline 200 mg twice daily Receives: Drug: Doxycycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
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.
Measured: Three months
Secondary outcomes (1)
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.
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2014 (estimated)
- Study startMar 2014
- Primary completionJul 2015
- Study completionNov 2015
Why it stopped: Lack of accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by University of RochesterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carla Casulo, University of Rochester
- Investigators
- Carla Casulo, MD, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02086591
- Sponsor's protocol ID
- 50370
- Other IDs
- 120145
- Status last verified
- Oct 2016
- First submitted
- 26 Feb 2014
- Last updated
- 22 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Doxycycline in Relapsed NHL
- ClinicalTrials.gov ID
- NCT02086591
- Acronym / sponsor ID
- 50370
- Conditions
- Adult Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma Recurrent, Lymphoma, Follicular, Marginal Zone B-Cell Lymphoma, Malignant Lymphoma - Lymphoplasmacytic, Waldenstrom Macroglobulinemia
- Keywords
- Non Hodgkin Lymphoma, Doxycycline
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of accrual
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- Mar 2014
- Primary completion
- Jul 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 13 Mar 2014 (estimated)
- Results
- Posted 22 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Doxycycline | Experimental | Drug: DoxycyclineDoxycycline 200 mg twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Doxycycline | Drug | Doxycycline |
Primary outcome
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.
1 secondary outcome
Percentage of Patients With Progression Free Survival
Time frame: One year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Carla Casulo, MD principal investigator
University of Rochester
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Doxycycline in people with Adult Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma Recurrent, run by University of Rochester at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: Three months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2016; AzTrials last refreshed its copy on 6 Nov 2026.