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

Diffuse Large B-Cell Lymphoma Clinical Trial

— DLBCL  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02531308
• Other study ID #: LYM2014-MET-R-CHOP | 15100503
• Status: Terminated
• Phase: Phase 2
• Start date: July 2015
• Est. completion date: July 2016

Study information

• Verified date: September 2022
• Source: Rush University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Metformin
Metformin upregulates AMPK activity which has been shown to have an anti-proliferative effect on lymphoma cells.
• Rituximab
monoclonal antibody against protein CD20 primarily found on the surface of B-cells
• Cyclophosphamide
Interferes with DNA replication
• Doxorubicin
anthracycline antitumor antibiotic
• Vincristine
Inhibits cell mitosis causing cell death.
• Prednisone
a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases
• pegfilgrastim
stimulates the level of white blood cells (neutrophils).

Locations

Country	Name	City	State
United States	Rush University Medical Center	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Rush University Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	rate of progression in patients 2 years after diagnosis	2 year