Back to resultsDA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma (DLBCL)
Primary Purpose
Diffuse Large B-Cell Lymphoma
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Metformin
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring Double Hit DLBCL
Eligibility Criteria
Inclusion Criteria:
- 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)
- 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)
Exclusion Criteria
- 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.
- 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 -
Sites / Locations
- Rush University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm, open label
Arm Description
Metformin added to standard of care treatment for all patients
Outcomes
Primary Outcome Measures
Evaluation of Impact of Metformin on 18 Month Progression-free Survival
Progression-free survival determined by CT scans at 18 months
Secondary Outcome Measures
Effect of Metformin Overall Response Rate
Evaluation of the effect of the addition of metformin to induction chemotherapy on overall response rates
Effect of Metformin Overall Survival
Evaluation of the addition of metformin to standard induction therapy on 18 month overall survival
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.
Full Information
NCT ID
NCT02815397
First Posted
May 17, 2016
Last Updated
October 17, 2017
Sponsor
Rush University Medical Center
Collaborators
Elsa U. Pardee Foundation
1. Study Identification
Unique Protocol Identification Number
NCT02815397
Brief Title
DA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma
Acronym
DLBCL
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2016
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual
Study Start Date
February 2016 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rush University Medical Center
Collaborators
Elsa U. Pardee Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-Cell Lymphoma
Keywords
Double Hit DLBCL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm, open label
Arm Type
Experimental
Arm Description
Metformin added to standard of care treatment for all patients
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Glumetza, Fortamet, Glucophage, Riomet
Intervention Description
given in addition to standard of care treatment
Primary Outcome Measure Information:
Title
Evaluation of Impact of Metformin on 18 Month Progression-free Survival
Description
Progression-free survival determined by CT scans at 18 months
Time Frame
18 month
Secondary Outcome Measure Information:
Title
Effect of Metformin Overall Response Rate
Description
Evaluation of the effect of the addition of metformin to induction chemotherapy on overall response rates
Time Frame
3 years
Title
Effect of Metformin Overall Survival
Description
Evaluation of the addition of metformin to standard induction therapy on 18 month overall survival
Time Frame
18 months
Title
Safety Profile With Addition of Metformin Evaluated by Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v.4.0
Description
Describe the safety profile observed by measuring fasting glucose and anion gap weekly through cycle 6.
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
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)
Exclusion Criteria
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.
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 -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reem Karmali, MD
Organizational Affiliation
Rush Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
DA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma
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