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

A Phase ll Study Evaluating the Efficacy and Safety of Metformin in Combination With Standard Induction Therapy (RM-CHOP) for Previously Untreated Aggressive Diffuse Large B-cell Lymphoma

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)

Study Overview

• Status: Terminated
• Conditions: Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: Metformin; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: pegfilgrastim

Detailed Description

Newly diagnosed histologically confirmed CD20 positive previously untreated diffuse large B-cell lymphoma to receive up to 4-6 cycles (21 day cycles) of:

R-CHOP: 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 IV Day 1 (cap @ 2mg) Prednisone 100mg PO daily Days 1-5 Pegfilgrastim 6 mg subcutaneously within 72 if start if cycle Metformin 500 mg PO daily Cycle 1 Days 1-7 Metformin 500 mg PO twice daily Cycle 1 Days 7-21 Metformin 850 mg PO twice daily starting on day 22 and and continuing throughout remainder of cycles plus 22 days post treatment.

Restaging will be done after the 4th cycle is complete. Subjects will be monitored with labs and physical exams throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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

2. No prior therapy for diagnosis of DLBCL
3. 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
4. Eastern Cooperative Oncology Group performance score of 0-2
5. Life expectancy of at least 6 months
6. No history of medication dependent diabetes mellitus
7. Required screening laboratory data (within 4 weeks prior to start of study drug) -

Exclusion Criteria:

1. 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
2. Known histological transformation from indolent non-Hodgkins Lymphoma (NHL) or chronic lymphocytic leukemia (CLL) to an aggressive form of NHL (ie, Richter transformation)
3. Double or triple hit lymphomas
4. Known active cent4ral nervous system or leptomeningeal lymphoma
5. Presence of known intermediate or high-grade myelodysplastic syndrome
6. History of a non-lymphoid malignancy within the last 3 years (see protocol for exceptions)
7. Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study
8. 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.
9. HIV positive
10. Ongoing inflammatory bowel disease
11. Ongoing alcohol or drug addiction
12. Pregnancy

13. History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.

    -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: R-CHOP with Metformin; 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; Metformin upregulates AMPK activity which has been shown to have an anti-proliferative effect on lymphoma cells.; Other Names: Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet.; Drug: Rituximab; monoclonal antibody against protein CD20 primarily found on the surface of B-cells; Other Names: Rituxan, Zytux, Mab thera; Drug: Cyclophosphamide; Interferes with DNA replication; Other Names: Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin; Drug: Doxorubicin; anthracycline antitumor antibiotic; Other Names: Adriamycin; Drug: Vincristine; Inhibits cell mitosis causing cell death.; Other Names: Oncovin; Drug: Prednisone; a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases; Other Names: Deltasone; Drug: pegfilgrastim; stimulates the level of white blood cells (neutrophils).; Other Names: Neulasta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	rate of progression in patients 2 years after diagnosis	2 year

Collaborators and Investigators

• Sponsor: Rush University Medical Center
• Investigators: Principal Investigator: Reem Karmali, MD, Assistant Professor of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: August 21, 2015
• First Posted (Estimate): August 24, 2015

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 21, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: lymphoma; diffuse large b-cell lymphoma (DLBCL),
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Metformin; Doxorubicin; Vincristine
• Other Study ID Numbers: LYM2014-MET-R-CHOP | 15100503

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided