Clinical Trials /

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

NCT02531308

Description:

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)

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Metformin</span> in Combination With Standard Induction Therapy for Large B-cell Lymphoma (DLBCL)

Title

  • Brief Title: Metformin in Combination With Standard Induction Therapy for Large B-cell Lymphoma (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 IDs

    NCT ID: NCT02531308

    ORG ID: LYM2014-MET-R-CHOP

    Trial Conditions

    Diffuse Large B-Cell Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    Metformin Glucophage, Glucophage XR, Glumetza, Fortamet, Riomet. R-CHOP with Metformin
    Rituximab Rituxan, Zytux, Mab thera R-CHOP with Metformin
    Cyclophosphamide Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cycloblastin R-CHOP with Metformin
    Doxorubicin Adriamycin R-CHOP with Metformin
    Vincristine Oncovin R-CHOP with Metformin
    Prednisone Deltasone R-CHOP with Metformin
    pegfilgrastim Neulasta R-CHOP with Metformin

    Trial Purpose

    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.

    Trial Arms

    Name Type Description Interventions
    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. Metformin, Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone, pegfilgrastim

    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

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    progression free survival

    Secondary Outcome Measures

    Trial Keywords

    diffuse large b-cell lymphoma (DLBCL),

    lymphoma