Diffuse Large B-Cell LymphomaPhase 2DLBCLNCT02531308
Metformin in Combination With Standard Induction Therapy for Large B-cell Lymphoma (DLBCL)
A Phase 2 study testing Metformin, Rituximab and Cyclophosphamide in people with Diffuse Large B-Cell Lymphoma, run by Rush University Medical Center at 1 site in United States.
Trial summary
Evaluation of impact of metformin on 2 year progression-free survival (PFS) rate in subjects with previously untreated DLBCL when added to standard induction therapy. (R-CHOP) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma
- What is being tested?
- Metformin, Rituximab and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2015to Jul 2016
- 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
- Diagnosis of Diffuse Large B-cell Lymphoma (DLBCL) as documented by medical records and with histology based on criteria established by the World Health Organization
- subtyping is required for DLBCL
- No prior therapy for diagnosis of DLBCL
- Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of equal to or greater than 1 lesion that measures >1.5 cm in the longest diameter and > 1.0 cm in the longest perpendicular diameter assessed by CT or MRI) or bone marrow involvement
- Eastern Cooperative Oncology Group performance score of 0-2
- Life expectancy of at least 6 months
- No history of medication dependent diabetes mellitus
- Required screening laboratory data (within 4 weeks prior to start of study drug) -
Who cannot join
- Patients already on any class of anti-diabetic medication including metformin, insulin analogues, sulfonylureas, thiazolidinediones (TZDs) and the incretin-based therapies or clear need for therapeutic intervention based on fasting blood glucose
- Known histological transformation from indolent non-Hodgkins Lymphoma (NHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of NHL (ie, Richter transformation)
- Double or triple hit lymphomas
- Known active cent4ral nervous system or leptomeningeal lymphoma
- Presence of known intermediate or high-grade myelodysplastic syndrome
- History of a non-lymphoid malignancy within the last 3 years (see protocol for exceptions)
Show all 14Show fewer
- Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study
- Ongoing, drug-induced liver injury, chronic active Hepatitis C Virus (HCV), chronic active Hepatitis B Virus (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
- HIV positive
- Ongoing inflammatory bowel disease
- Ongoing alcohol or drug addiction
- Pregnancy
- History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Rush University Medical Center
Chicago, Illinois, 60612
About this study
Official title: A Phase ll Study Evaluating the Efficacy and Safety of Metformin in Combination With Standard Induction Therapy (RM-CHOP) for Previously Untreated Aggressive Diffuse Large B-cell Lymphoma
Evaluation of impact of metformin on 2 year progression-free survival (PFS) rate in subjects with previously untreated DLBCL when added to standard induction therapy. (R-CHOP)
Read the detailed description
Newly diagnosed histologically confirmed CD20 positive previously untreated diffuse large B-cell lymphoma to receive up to 4-6 cycles (21 day cycles) of:
R-CHOP: Rituximab 375 mg/m2 IV infusion Day 1 Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 (cap @ 2mg) Prednisone 100mg PO daily Days 1-5 Pegfilgrastim 6 mg subcutaneously within 72 if start if cycle Metformin 500 mg PO daily Cycle 1 Days 1-7 Metformin 500 mg PO twice daily Cycle 1 Days 7-21 Metformin 850 mg PO twice daily starting on day 22 and and continuing throughout remainder of cycles plus 22 days post treatment.
Restaging will be done after the 4th cycle is complete. Subjects will be monitored with labs and physical exams throughout the study.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- Metformin, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine
- Keywords
- diffuse large b-cell lymphoma (DLBCL),, lymphoma
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Dendritic Cell Sarcoma, Interdigitating, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet.
Metformin upregulates AMPK activity which has been shown to have an anti-proliferative effect on lymphoma cells.
RituximabDrug
Also called Rituxan, Zytux, Mab thera
monoclonal antibody against protein CD20 primarily found on the surface of B-cells
CyclophosphamideDrug
Also called Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin
Interferes with DNA replication
DoxorubicinDrug
Also called Adriamycin
anthracycline antitumor antibiotic
VincristineDrug
Also called Oncovin
Inhibits cell mitosis causing cell death.
PrednisoneDrug
Also called Deltasone
a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases
pegfilgrastimDrug
Also called Neulasta
stimulates the level of white blood cells (neutrophils).
| Study group | Role | What they receive |
|---|---|---|
| R-CHOP with Metformin | Experimental | Rituximab 375 mg/m2 IV infusion Day 1 Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 (2 mg cap) IV Day 1 Prednisone 100 mg PO Days 1-5 Pegfilgrastim 6 mg subcutaneous within 72 hours of cyclophosphomide Metformin 500 mg PO daily D 1-7, 500 mg twice daily D8-21, 850 mg twice daily D22 - 30days post study.
Cycles are 21 days. Above treatment given for 4 cycles, then restaging done. If complete response (CR) or partial response (PR), 2 more cycle given; stable disease (SD) or progressive disease (PD)- salvage therapy off study. Receives: Drug: Metformin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: pegfilgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
rate of progression in patients 2 years after diagnosis
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2015 (estimated)
- Study startJul 2015
- Primary completionJul 2016
- Study completionJul 2016
Why it stopped: poor 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 Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Reem Karmali, MD, Principal investigator, Assistant Professor of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02531308
- Sponsor's protocol ID
- LYM2014-MET-R-CHOP | 15100503
- Acronym
- DLBCL
- Status last verified
- Sep 2022
- First submitted
- 27 Jul 2015
- Last updated
- 28 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase ll Study Evaluating the Efficacy and Safety of Metformin in Combination With Standard Induction Therapy (RM-CHOP) for Previously Untreated Aggressive Diffuse Large B-cell Lymphoma
- ClinicalTrials.gov ID
- NCT02531308
- Acronym / sponsor ID
- DLBCL / LYM2014-MET-R-CHOP | 15100503
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- diffuse large b-cell lymphoma (DLBCL),, lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Study start
- Jul 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 24 Aug 2015 (estimated)
- Results
- Posted 27 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluation of impact of metformin on 2 year progression-free survival (PFS) rate in subjects with previously untreated DLBCL when added to standard induction therapy. (R-CHOP)
Detailed description
Newly diagnosed histologically confirmed CD20 positive previously untreated diffuse large B-cell lymphoma to receive up to 4-6 cycles (21 day cycles) of:
R-CHOP: Rituximab 375 mg/m2 IV infusion Day 1 Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 IV Day 1 (cap @ 2mg) Prednisone 100mg PO daily Days 1-5 Pegfilgrastim 6 mg subcutaneously within 72 if start if cycle Metformin 500 mg PO daily Cycle 1 Days 1-7 Metformin 500 mg PO twice daily Cycle 1 Days 7-21 Metformin 850 mg PO twice daily starting on day 22 and and continuing throughout remainder of cycles plus 22 days post treatment.
Restaging will be done after the 4th cycle is complete. Subjects will be monitored with labs and physical exams throughout the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| R-CHOP with Metformin | Experimental | Drug: Metformin, Drug: Rituximab, Drug: Cyclophosphamide, Drug: Doxorubicin, Drug: Vincristine, Drug: Prednisone, Drug: pegfilgrastimRituximab 375 mg/m2 IV infusion Day 1 Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Vincristine 1.4 mg/m2 (2 mg cap) IV Day 1 Prednisone 100 mg PO Days 1-5 Pegfilgrastim 6 mg subcutaneous within 72 hours of cyclophosphomide Metformin 500 mg PO daily D 1-7, 500 mg twice daily D8-21, 850 mg twice daily D22 - 30days post study. Cycles are 21 days. Above treatment given for 4 cycles, then restaging done. If complete response (CR) or partial response (PR), 2 more cycle given; stable disease (SD) or progressive disease (PD)- salvage therapy off study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of Diffuse Large B-cell Lymphoma (DLBCL) as documented by medical records and with histology based on criteria established by the World Health Organization
- No prior therapy for diagnosis of DLBCL
- Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of equal to or greater than 1 lesion that measures >1.5 cm in the longest diameter and > 1.0 cm in the longest perpendicular diameter assessed by CT or MRI) or bone marrow involvement
- Eastern Cooperative Oncology Group performance score of 0-2
- Life expectancy of at least 6 months
Key exclusion criteria (14 listed)
- Patients already on any class of anti-diabetic medication including metformin, insulin analogues, sulfonylureas, thiazolidinediones (TZDs) and the incretin-based therapies or clear need for therapeutic intervention based on fasting blood glucose
- Known histological transformation from indolent non-Hodgkins Lymphoma (NHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of NHL (ie, Richter transformation)
- Double or triple hit lymphomas
- Known active cent4ral nervous system or leptomeningeal lymphoma
- Presence of known intermediate or high-grade myelodysplastic syndrome
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 |
|---|---|---|
| MetforminAlso: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet.Metformin upregulates AMPK activity which has been shown to have an anti-proliferative effect on lymphoma cells. | Drug | R-CHOP with Metformin |
| RituximabAlso: Rituxan, Zytux, Mab theramonoclonal antibody against protein CD20 primarily found on the surface of B-cells | Drug | R-CHOP with Metformin |
| CyclophosphamideAlso: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, CycloblastinInterferes with DNA replication | Drug | R-CHOP with Metformin |
| DoxorubicinAlso: Adriamycinanthracycline antitumor antibiotic | Drug | R-CHOP with Metformin |
| VincristineAlso: OncovinInhibits cell mitosis causing cell death. | Drug | R-CHOP with Metformin |
| PrednisoneAlso: Deltasonea synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases | Drug | R-CHOP with Metformin |
| pegfilgrastimAlso: Neulastastimulates the level of white blood cells (neutrophils). | Drug | R-CHOP with Metformin |
Primary outcome
Progression Free Survival
Time frame: 2 year
rate of progression in patients 2 years after diagnosis
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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.
Reem Karmali, MD principal investigator
Assistant Professor of Medicine
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 Metformin, Rituximab and Cyclophosphamide in people with Diffuse Large B-Cell Lymphoma, run by Rush University Medical Center 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 8 inclusion and 14 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 28 Sep 2022. 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 27 Jan 2017). 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?
Progression Free Survival (time frame: 2 year). 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 28 Sep 2022.