Diffuse Large B-Cell LymphomaPhase 2DLBCLNCT02815397
DA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma
A Phase 2 study testing Metformin in people with Diffuse Large B-Cell Lymphoma, run by Rush University Medical Center at 1 site in United States.
Trial summary
Newly diagnosed histologically confirmed c-myc+ de novo DLBCL. Metformin 500 mg daily x 1 week, then 500 mg twice daily (BID) x 2 weeks, then 850 mg twice daily until 1 month after last cycle of chemo-immunotherapy. 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
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2016to 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
- Male or female ≥ 18 years of age
- Diagnosis of DLBCL as documented by medical records and with histology based on criteria established by the World Health Organization
- subtyping is required for DLBCL
- c-myc+ defined as presence of c-myc breaks by karyotype/FISH and/or IHC ≥ 40%; this includes double hits (with bcl-2 breaks found using cytogenetics/FISH) and/or double expressors (with bcl-2 protein expression ≥ 70% by IHC); increased copy number in itself is not considered positivity for c-myc
- No prior therapy for diagnosis of DLBCL with exception of steroids
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0- 2 (Appendix B)
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- Life expectancy of at least 6 months
- No history of medication dependent diabetes mellitus
- No evidence of acute or chronic metabolic acidosis (baseline venous lactate ≤ 4)
Who cannot join
- Patient 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-Hodgkin Lymphoma (iNHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of non-Hodgkin's lymphoma (NHL) (ie, Richter transformation)
- Burkitt and/or precursor lymphoblastic leukemia/lymphoma.
- Presence of known intermediate- or high-grade myelodysplastic syndrome
- History of an active of treated non-lymphoid malignancy within the last 3 years excluding basal cell and squamous cell skin cancers
- Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study drug.
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- Subjects who have currently active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver involvement with NHL or stable chronic liver disease per investigator assessment)
- Renal insufficiency with creatinine > 1.5 x upper limit of normal (ULN) OR creatinine clearance of < 45 ml/min as calculated by the Cockcroft-Gault method
- CNS or leptomeningeal involvement of lymphoma
- HIV positive
- Ongoing inflammatory bowel disease
- Ongoing alcohol or drug addiction
- Pregnancy or breastfeeding
- 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: DA-EPOCH-RM: A Phase II Study Evaluating the Efficacy and Safety of Metformin in Combination With Standard Induction Therapy (DA-EPOCH-R) for Previously Untreated C-myc+ Diffuse Large B-Cell Lymphoma
Newly diagnosed histologically confirmed c-myc+ de novo DLBCL. Metformin 500 mg daily x 1 week, then 500 mg twice daily (BID) x 2 weeks, then 850 mg twice daily until 1 month after last cycle of chemo-immunotherapy.
DA-EPOCH-R every 21 days x 4 cycles (CNS prophylaxis single or triple therapy given intrathecally each cycle to patients deemed appropriate by treating physician).
Restage after 4 cycles with CT. Complete remission or partial remission: complete 2 more cycles or radiation therapy (XRT) consolidation per physician. Stable or progressive disease will go on to salvage therapy off study.
Read the detailed description
Subject admitted to in-patient care for day 1 or each cycle and discharged on day 5. On day 6, subject receives Rituximab in outpatient infusion facility.
Metformin is dispensed on day 1 of each cycle and taken as follows: Cycle 1 days 1-7 500 mg daily. Days 8-21, 500 mg twice daily. Cycle 2 through end of treatment, metformin given 850 mg twice daily.
Inpatient treatment: DA-EPOCH every 21 days Etoposide (VP-16) 50 mg/m2/d civi d1-4 (continuous infusion) Prednisone 60 mg/m2 BID po d1-5 Vincristine 0.4 mg/m2/d civi d 1-4 (continuous infusion) Doxorubicin (Adriamycin) 10 mg/m2/d civi d1-4 (continuous infusion) Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 min d5 If clinically indicated, patients who are deemed appropriate for central nervous system (CNS) prophylaxis by their treating physician will receive either single agent intrathecal methotrexate (12 mg) or triple therapy (15 mg methotrexate, 30 mg cytarabine, 30 mg hydrocortisone) with each cycle of chemotherapy.
Rituximab 375 mg/m2 IV every 21 days on D6-8 post DA-EPOCH (per standard institutional guidelines) DA-dose adjustment paradigm based on twice weekly complete blood count (CBC) (dose adjustment above starting doses apply to Etoposide (VP-16), Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan). If nadir absolute neutrophil count(ANC)>500/microliter (uL), 20% increase in all 3 drugs. If nadir<500/uL on 1 or 2 measurements, same doses as last cycle. If nadir <500/uL on at least 3 measurements, or nadir platelet <25,000/uL on 1 measurement, 20% decrease in Etoposide, Doxorubicin and Cyclophosphamide below last cycle.
Filgrastim (Neupogen) 5 mcg/kg sc qd beginning on d6 until ANC>5,000/uL or Pegfilgrastim (Neulasta) 6 mg sc 24-72 hours post chemotherapy.
Restaging with CT scans is done after cycle 4 and:
complete remission (CR)/partial remission (PR) - complete 2 more cycles of therapy OR consolidation radiation therapy per treating physician.
stable disease (SD)/progressive disease (PD) - salvage therapy off study.
- Conditions
- Diffuse Large B-Cell Lymphoma
- Being tested
- Metformin
- Keywords
- Double Hit DLBCL
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glumetza, Fortamet, Glucophage, Riomet
given in addition to standard of care treatment
| Study group | Role | What they receive |
|---|---|---|
| Single arm, open label | Experimental | Metformin added to standard of care treatment for all patients Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of Impact of Metformin on 18 Month Progression-free Survival
Progression-free survival determined by CT scans at 18 months
Measured: 18 month
Secondary outcomes (3)
Effect of Metformin Overall Response Rate
Evaluation of the effect of the addition of metformin to induction chemotherapy on overall response rates
Measured: 3 years
Effect of Metformin Overall Survival
Evaluation of the addition of metformin to standard induction therapy on 18 month overall survival
Measured: 18 months
Safety Profile With Addition of Metformin Evaluated by Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v.4.0
Describe the safety profile observed by measuring fasting glucose and anion gap weekly through cycle 6.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2016 (estimated)
- Study startFeb 2016
- 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.
- More trials run by Rush University Medical CenterThe 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rush University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Elsa U. Pardee Foundation
- Responsible party
- Sponsor
- Investigators
- Reem Karmali, MD, Principal investigator, Rush Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02815397
- Sponsor's protocol ID
- LYM15 DA-EPOCH-RM
- Acronym
- DLBCL
- Status last verified
- Dec 2016
- First submitted
- 17 May 2016
- Last updated
- 17 Nov 2017
- 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 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DA-EPOCH-RM: A Phase II Study Evaluating the Efficacy and Safety of Metformin in Combination With Standard Induction Therapy (DA-EPOCH-R) for Previously Untreated C-myc+ Diffuse Large B-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT02815397
- Acronym / sponsor ID
- DLBCL / LYM15 DA-EPOCH-RM
- Conditions
- Diffuse Large B-Cell Lymphoma
- Keywords
- Double Hit DLBCL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Rush University Medical CenterUniversity, hospital or other
- Collaborators
- Elsa U. Pardee Foundation
- Study start
- Feb 2016
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 28 Jun 2016 (estimated)
- Results
- Posted 17 Nov 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Newly diagnosed histologically confirmed c-myc+ de novo DLBCL. Metformin 500 mg daily x 1 week, then 500 mg twice daily (BID) x 2 weeks, then 850 mg twice daily until 1 month after last cycle of chemo-immunotherapy.
DA-EPOCH-R every 21 days x 4 cycles (CNS prophylaxis single or triple therapy given intrathecally each cycle to patients deemed appropriate by treating physician).
Restage after 4 cycles with CT. Complete remission or partial remission: complete 2 more cycles or radiation therapy (XRT) consolidation per physician. Stable or progressive disease will go on to salvage therapy off study.
Detailed description
Subject admitted to in-patient care for day 1 or each cycle and discharged on day 5. On day 6, subject receives Rituximab in outpatient infusion facility.
Metformin is dispensed on day 1 of each cycle and taken as follows: Cycle 1 days 1-7 500 mg daily. Days 8-21, 500 mg twice daily. Cycle 2 through end of treatment, metformin given 850 mg twice daily.
Inpatient treatment: DA-EPOCH every 21 days Etoposide (VP-16) 50 mg/m2/d civi d1-4 (continuous infusion) Prednisone 60 mg/m2 BID po d1-5 Vincristine 0.4 mg/m2/d civi d 1-4 (continuous infusion) Doxorubicin (Adriamycin) 10 mg/m2/d civi d1-4 (continuous infusion) Cyclophosphamide (Cytoxan) 750 mg/m2 IV over 15 min d5 If clinically indicated, patients who are deemed appropriate for central nervous system (CNS) prophylaxis by their treating physician will receive either single agent intrathecal methotrexate (12 mg) or triple therapy (15 mg methotrexate, 30 mg cytarabine, 30 mg hydrocortisone) with each cycle of chemotherapy.
Rituximab 375 mg/m2 IV every 21 days on D6-8 post DA-EPOCH (per standard institutional guidelines) DA-dose adjustment paradigm based on twice weekly complete blood count (CBC) (dose adjustment above starting doses apply to Etoposide (VP-16), Doxorubicin (Adriamycin) and Cyclophosphamide (Cytoxan). If nadir absolute neutrophil count(ANC)>500/microliter (uL), 20% increase in all 3 drugs. If nadir<500/uL on 1 or 2 measurements, same doses as last cycle. If nadir <500/uL on at least 3 measurements, or nadir platelet <25,000/uL on 1 measurement, 20% decrease in Etoposide, Doxorubicin and Cyclophosphamide below last cycle.
Filgrastim (Neupogen) 5 mcg/kg sc qd beginning on d6 until ANC>5,000/uL or Pegfilgrastim (Neulasta) 6 mg sc 24-72 hours post chemotherapy.
Restaging with CT scans is done after cycle 4 and:
complete remission (CR)/partial remission (PR) - complete 2 more cycles of therapy OR consolidation radiation therapy per treating physician.
stable disease (SD)/progressive disease (PD) - salvage therapy off study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arm, open label | Experimental | Drug: MetforminMetformin added to standard of care treatment for all patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female ≥ 18 years of age
- Diagnosis of 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 with exception of steroids
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0- 2 (Appendix B)
- Life expectancy of at least 6 months
Key exclusion criteria (14 listed)
- Patient 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-Hodgkin Lymphoma (iNHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of non-Hodgkin's lymphoma (NHL) (ie, Richter transformation)
- Burkitt and/or precursor lymphoblastic leukemia/lymphoma.
- Presence of known intermediate- or high-grade myelodysplastic syndrome
- History of an active of treated non-lymphoid malignancy within the last 3 years excluding basal cell and squamous cell skin cancers
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: Glumetza, Fortamet, Glucophage, Riometgiven in addition to standard of care treatment | Drug | Single arm, open label |
Primary outcome
Evaluation of Impact of Metformin on 18 Month Progression-free Survival
Time frame: 18 month
Progression-free survival determined by CT scans at 18 months
3 secondary outcomes
Effect of Metformin Overall Response Rate
Time frame: 3 years
Effect of Metformin Overall Survival
Time frame: 18 months
Safety Profile With Addition of Metformin Evaluated by Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v.4.0
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2017.
- 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
Rush Medical Center
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 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 9 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 17 Nov 2017. 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 17 Nov 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?
Evaluation of Impact of Metformin on 18 Month Progression-free Survival (time frame: 18 month). 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 17 Nov 2017.