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

NCT02815397 | Terminated Phase 2 Results DMC

• 1 other identifier: LYM15 DA-EPOCH-RM
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

Double Hit DLBCL

Outcome Measures

Primary Outcomes (1)

• Evaluation of Impact of Metformin on 18 Month Progression-free Survival

  Progression-free survival determined by CT scans at 18 months

  18 month

Secondary Outcomes (3)

• Effect of Metformin Overall Response Rate

  3 years

• Effect of Metformin Overall Survival

  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

  18 months

Study Arms (1)

Single arm, open label

EXPERIMENTAL

Metformin added to standard of care treatment for all patients

Drug: Metformin

Interventions

Metformin DRUG

given in addition to standard of care treatment

Also known as: Glumetza, Fortamet, Glucophage, Riomet

Single arm, open label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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 -

Sponsors & Collaborators

• Rush University Medical Center: lead
• Elsa U. Pardee Foundation: collaborator

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

Metformin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

Study closed prematurely - will not be able to report on any PFS, OS, ORR. Will not have any additional information on adverse events/toxicity

Results Point of Contact

• Title: Dr. R Karmali
• Organization: Northwestern University

reem.karmali@northwestern.edu

312-695-6832

Study Officials

• Reem Karmali, MD

  Rush Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: June 28, 2016
• Study Start: February 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: November 17, 2017
• Results First Posted: November 17, 2017

Record last verified: 2016-12

Locations

US (1)