Metformin in Combination With Standard Induction Therapy for Large B-cell Lymphoma (DLBCL)

NCT02531308 | Terminated Phase 2 Results DMC

• 1 other identifier: LYM2014-MET-R-CHOP | 15100503
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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)

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

diffuse large b-cell lymphoma (DLBCL),; lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  rate of progression in patients 2 years after diagnosis

  2 year

Study Arms (1)

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.

Drug: Metformin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: pegfilgrastim

Interventions

Metformin DRUG

Metformin upregulates AMPK activity which has been shown to have an anti-proliferative effect on lymphoma cells.

Also known as: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet.

R-CHOP with Metformin

Rituximab DRUG

monoclonal antibody against protein CD20 primarily found on the surface of B-cells

Also known as: Rituxan, Zytux, Mab thera

R-CHOP with Metformin

Cyclophosphamide DRUG

Interferes with DNA replication

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin

R-CHOP with Metformin

Doxorubicin DRUG

anthracycline antitumor antibiotic

Also known as: Adriamycin

R-CHOP with Metformin

Vincristine DRUG

Inhibits cell mitosis causing cell death.

Also known as: Oncovin

R-CHOP with Metformin

Prednisone DRUG

a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases

Also known as: Deltasone

R-CHOP with Metformin

pegfilgrastim DRUG

stimulates the level of white blood cells (neutrophils).

Also known as: Neulasta

R-CHOP with Metformin

Eligibility Criteria

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

You may qualify if:

• 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
• a. 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) -

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Rush University Medical Center: lead

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Dendritic Cell Sarcoma, Interdigitating; Lymphoma

Interventions

Metformin; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; pegfilgrastim

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Limitations and Caveats

Unable to report on endpoint of 2 year PFS as trial prematurely terminated

Results Point of Contact

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

reem.karmali@northwestern.edu

312-695-0686

Study Officials

• Reem Karmali, MD

  Assistant Professor of Medicine

  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: July 27, 2015
• First Posted: August 24, 2015
• Study Start: July 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: September 28, 2022
• Results First Posted: January 27, 2017

Record last verified: 2022-09

Locations

US (1)