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

NCT ID: NCT02531308

Last Updated: 2022-09-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2016-07-31

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)

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.

Conditions

Diffuse Large B-Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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

Rituximab

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

Interferes with DNA replication

Doxorubicin

Intervention Type: DRUG

anthracycline antitumor antibiotic

Vincristine

Intervention Type: DRUG

Inhibits cell mitosis causing cell death.

Prednisone

Intervention Type: DRUG

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

pegfilgrastim

Intervention Type: DRUG

stimulates the level of white blood cells (neutrophils).

Interventions

Metformin

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

Intervention Type: DRUG

Rituximab

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

Intervention Type: DRUG

Cyclophosphamide

Interferes with DNA replication

Intervention Type: DRUG

Doxorubicin

anthracycline antitumor antibiotic

Intervention Type: DRUG

Vincristine

Inhibits cell mitosis causing cell death.

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

pegfilgrastim

stimulates the level of white blood cells (neutrophils).

Intervention Type: DRUG

Other Intervention Names

Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet.; Rituxan, Zytux, Mab thera; Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin; Adriamycin; Oncovin; Deltasone; Neulasta

Eligibility Criteria

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.

-

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rush University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Reem Karmali, MD

Role: PRINCIPAL_INVESTIGATOR

Assistant Professor of Medicine

Locations

Rush University Medical Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

LYM2014-MET-R-CHOP | 15100503

Identifier Type: -

Identifier Source: org_study_id