DA-EPOCH-Rituximab/Metformin (RM) for Double Hit Lymphoma

• Status: Terminated
• Trial end date: 2016-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rush University Medical Center
• Collaborators: Elsa U. Pardee Foundation; Pardee Foundation
• Treatments: Metformin

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 -