Clinical Trials /

Polatuzumab Vedotin and Combination Chemotherapy for the Treatment of Untreated Aggressive Large B-cell Lymphoma

NCT04231877

Description:

This trial studies the side effects of polatuzumab vedotin when given with combination chemotherapy for the treatment of patients with untreated large B-cell lymphoma that grows and spreads quickly and has severe symptoms (aggressive). Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in combination chemotherapy such as etoposide, prednisone, cyclophosphamide, doxorubicin and rituximab work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving polatuzumab vedotin in addition to etoposide, prednisone, cyclophosphamide, doxorubicin and rituximab may help treat patients with aggressive large B-cell lymphoma.

Related Conditions:
  • ALK-Positive Large B-Cell Lymphoma
  • B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Double-Hit Lymphoma
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal B-Cell Lymphoma
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
  • Triple-Hit Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Polatuzumab Vedotin and Combination Chemotherapy for the Treatment of Untreated Aggressive Large B-cell Lymphoma
  • Official Title: A Pilot Study to Estimate the Safety and Tolerability of the Combination of Polatuzumab Vedotin With Dose Adjusted Rituximab, Etoposide, Cyclophosphamide, and Doxorubicin (DA-EPCH-PR) for Upfront Treatment of Aggressive B-Cell Non-Hodgkin Lymphomas

Clinical Trial IDs

  • ORG STUDY ID: RG1006477
  • SECONDARY ID: NCI-2019-08983
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT04231877

Conditions

  • Aggressive Non-Hodgkin Lymphoma
  • ALK-Positive Large B-Cell Lymphoma
  • B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • EBV-Positive Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Primary Mediastinal (Thymic) Large B-Cell Lymphoma
  • T-Cell/Histiocyte-Rich Large B-Cell Lymphoma

Interventions

DrugSynonymsArms
Polatuzumab Vedotin1313206-42-6, ADC DCDS4501A, Antibody-Drug Conjugate DCDS4501A, DCDS4501A, FCU 2711, polatuzumab vedotin-piiq, Polivy, RG7596, Ro 5541077-000Treatment (polatuzumab vedotin, combination chemotherapy)
Rituximab174722-31-7, 687451, ABP 798, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-C2B8 Monoclonal Antibody, Rituxan, Rituximab ABBS, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, rituximab-abbsTreatment (polatuzumab vedotin, combination chemotherapy)
Prednisone2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Metacortandracin, Meticorten, Ofisolona, Panafcort, Paracort, Predicor, Predicorten, Prednidib, Prednilonga, PrednitoneTreatment (polatuzumab vedotin, combination chemotherapy)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, VepesidTreatment (polatuzumab vedotin, combination chemotherapy)
DoxorubicinAdriablastin, Hydroxydaunomycin, Hydroxyl DaunorubicinTreatment (polatuzumab vedotin, combination chemotherapy)
CyclophosphamideCarloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, CyclostinTreatment (polatuzumab vedotin, combination chemotherapy)
FilgrastimG-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, TevagrastimTreatment (polatuzumab vedotin, combination chemotherapy)

Purpose

This trial studies the side effects of polatuzumab vedotin when given with combination chemotherapy for the treatment of patients with untreated large B-cell lymphoma that grows and spreads quickly and has severe symptoms (aggressive). Polatuzumab vedotin is a monoclonal antibody, polatuzumab, linked to a toxic agent called vedotin. Polatuzumab attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Drugs used in combination chemotherapy such as etoposide, prednisone, cyclophosphamide, doxorubicin and rituximab work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving polatuzumab vedotin in addition to etoposide, prednisone, cyclophosphamide, doxorubicin and rituximab may help treat patients with aggressive large B-cell lymphoma.

Detailed Description

      OUTLINE:

      Patients receive rituximab intravenously (IV) on day 1, polatuzumab vedotin IV on day 1,
      prednisone orally (PO) twice daily (BID) on days 1-5, etoposide IV on days 1-4, doxorubicin
      IV on days 1-4, and cyclophosphamide IV on day 5. Patients also receive filgrastim
      subcutaneously (SC) 24-72 hours after the last dose of each treatment cycle. Treatment
      repeats every 21 days for up to 6 cycles in the absence of disease progression or
      unacceptable toxicity.

      After the completion of study treatment, patients are followed periodically for up to 5
      years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (polatuzumab vedotin, combination chemotherapy)ExperimentalPatients receive rituximab IV on day 1, polatuzumab vedotin IV on day 1, prednisone PO BID on days 1-5, etoposide IV on days 1-4, doxorubicin IV on days 1-4, and cyclophosphamide IV on day 5. Patients also receive filgrastim SC 24-72 hours after the last dose of each treatment cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
  • Polatuzumab Vedotin
  • Rituximab
  • Prednisone
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Filgrastim

Eligibility Criteria

        Inclusion Criteria:

          -  Untreated aggressive B-cell large-B cell lymphoma (non-Hodgkin lymphoma) with adverse
             features that may predict sub-optimal response to rituximab-cyclophosphamide,
             doxorubicin (hydroxydaunorubicin), vincristine (Oncovin), prednisone (R-CHOP) and in
             the opinion of the investigator would be treated with DA-EPOCH-R as standard of care.
             Subjects must be planned to receive full course (6 cycles) chemoimmunotherapy as per
             clinical standard of care. Composite lymphomas are not excluded provided that the
             subject has not receive prior systemic therapy for the indolent component and would
             receive DA-EPOCH-R as the standard of care regimen for the aggressive component.
             Eligible histologies based on 2016 World Health Organisation (WHO) classification
             include:

               -  High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations

               -  High grade B-cell lymphoma, not otherwise specified (NOS)

               -  Diffuse large B-cell lymphoma (DLBCL) NOS

               -  Primary mediastinal B-cell lymphoma

               -  T-cell/histiocyte-rich large-B-cell lymphoma

               -  Epstein-Barr virus (EBV) + DLBCL, NOS

               -  ALK+ large B-cell lymphoma

               -  B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and
                  classical Hodgkin lymphoma

          -  Be willing and able to provide written informed consent for the trial.

          -  Have measurable nodal disease, including at least 1 disease site measuring 1.5 cm in
             longest dimension on computed tomography (CT) or fluorodeoxyglucose-positron emission
             tomography (FDG-PET)

          -  Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)
             performance scale (PS)

          -  Left ventricular ejection fraction (LVEF) >= 50% on cardiac multiple-gated acquisition
             (MUGA) scan or cardiac echocardiogram (ECHO)

          -  Absolute neutrophil count (ANC) >= 1,000/uL except in cases of marrow infiltration by
             lymphoma

          -  Platelets >= 75,000 / mcL except in cases of marrow infiltration by lymphoma or
             hypersplenism

          -  Hemoglobin >= 8 g/dL except in cases of marrow infiltration by lymphoma without red
             blood cell (RBC) transfusion within 14 days of first treatment

          -  Measured or calculated creatinine clearance (Glomerular filtration rate [GFR] can also
             be used in place of creatinine or creatinine clearance [CrCl]) >= 40 mL/min.

             * Creatinine clearance should be calculated per institutional standard

          -  Serum total bilirubin =< 1.5 X upper limit of normal (ULN) (Patients with documented
             Gilbert disease may be enrolled if total bilirubin =< 3.0 x ULN)

          -  Direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X
             ULN OR =< 5 X ULN for subjects with liver involvement

          -  International Normalized Ratio (INR) or Prothrombin Time (PT) =< 1.5 X ULN unless
             subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
             time (PTT) is within therapeutic range of intended use of anticoagulants

          -  Activated partial thromboplastin time (aPTT) =<1.5 X ULN unless subject is receiving
             anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
             of anticoagulants, or subject is shown to have an antiphospholipid antibody on workup

          -  For women of childbearing potential: agreement to remain abstinent (refrain from
             heterosexual intercourse) or use contraceptive methods that result in a failure rate
             of =< 1% per year during the treatment period and for at least 12 months after the
             last dose of study treatment. Women must refrain from donating eggs during this same
             period. A woman is considered to be of childbearing potential if she is
             post-menarcheal, has not reached a postmenopausal state (=<12 continuous months of
             amenorrhea with no identified cause other than menopause), and has not undergone
             surgical sterilization (removal of ovaries and/or uterus). The definition of
             childbearing potential may be adapted for alignment with local guidelines or
             requirements. Examples of contraceptive methods with a failure rate of =<1% per year
             include bilateral tubal ligation, male sterilization, hormonal contraceptives that
             inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine
             devices. The reliability of sexual abstinence should be evaluated in relation to the
             duration of the clinical trial and the preferred and usual lifestyle of the patient.
             Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation
             methods) and withdrawal are not acceptable methods of contraception

          -  For women of childbearing potential, a negative serum pregnancy test result during
             screening period. Women who are considered not to be of childbearing potential are not
             required to have a pregnancy test

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             a condom, and agreement to refrain from donating sperm, as defined below: With female
             partners of childbearing potential or pregnant female partners, men must remain
             abstinent or use a condom during the treatment period and for at least 5 months after
             the last treatment. Men must refrain from donating sperm during this same period. The
             reliability of sexual abstinence should be evaluated in relation to the duration of
             the clinical trial and the preferred and usual lifestyle of the patient. Periodic
             abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and
             withdrawal are not acceptable methods of preventing drug exposure. Male patients
             considering preservation of fertility should bank sperm before study treatment

        Exclusion Criteria:

          -  Contraindication to any of the individual components of EPCH-R, including prior
             receipt of anthracyclines, or history of severe allergic or anaphylactic reactions to
             humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine
             products

          -  Prior systemic treatment for lymphoma with the exception of corticosteroids. Prior
             radiotherapy is allowed provided that this site is not used as a measurable site to
             assess response.

          -  Richter's transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma
             is not allowed. Transformation from follicular lymphoma is allowed provided that the
             subject has not received prior systemic therapy for their lymphoma and the aggressive
             component meets one of the criteria listed in inclusion criterion 1

          -  Diagnosis of Burkitt lymphoma

          -  Prior organ transplantation

          -  Current Grade > 1 peripheral neuropathy by clinical examination or demyelinating form
             of Charcot-Marie-Tooth disease

          -  Prior systemic therapy for indolent lymphoma

          -  Prior use of any monoclonal antibody within 3 months of the start of cycle 1; any
             investigational therapy within 28 days prior to the start of cycle 1; vaccination with
             live vaccines within 28 days prior the start of cycle 1

          -  Prior therapy for large B-cell lymphoma except for patients who require lymphoma
             symptom control during screening may receive steroids in the following manner: Up to
             30 mg/day of prednisone or equivalent may be used for lymphoma symptom control during
             screening, including prior to finalization of staging (not included as part of
             pre-phase treatment) If glucocorticoid treatment is urgently required at higher doses
             for lymphoma symptom control prior to the start of study treatment, tumor assessments
             must be completed prior to initiation of > 30-100 mg/day of prednisone or equivalent.
             Prednisone > 30-100 mg/day or equivalent may be given for a maximum of 7 days as a
             pre-phase treatment.

          -  History of other malignancy that could affect compliance with the protocol or
             interpretation of results except with permission of the principal investigator. The
             following are eligible without a specific waiver:

               -  Patients with a history of curatively treated basal or squamous cell carcinoma or
                  melanoma of the skin or in situ carcinoma of the cervix at any time prior to the
                  study are eligible

               -  Patients with any malignancy appropriately treated with curative intent and the
                  malignancy has been in remission without treatment for >= 2 years prior to
                  enrollment are eligible

               -  Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below,
                  Stage 1 or 2) with no requirement for therapy at any time prior to study are
                  eligible

          -  Evidence of significant, uncontrolled, concomitant diseases that could affect
             compliance with the protocol or interpretation of results, including significant
             cardiovascular disease (such as New York Heart Association Class III or IV cardiac
             disease, myocardial infarction within the last 6 months, unstable arrhythmias, or
             unstable angina) or pulmonary disease (including obstructive pulmonary disease and
             history of bronchospasm)

          -  Recent major surgery (within 4 weeks prior to the start of cycle 1), other than for
             diagnosis

          -  History or presence of an abnormal electrocardiogram (ECG) that is clinically
             significant in the investigator's opinion, including complete left bundle branch
             block, second- or third-degree heart block, or evidence of prior myocardial infarction

          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
             (excluding fungal infections of nail beds) which requires systemic treatment. Patients
             may proceed with screening during treatment for infection, but systemic treatment must
             be completed by cycle 1 day 1

          -  Positive test results for chronic hepatitis B infection (defined as positive hepatitis
             B surface antigen [HBsAg] serology):

             * Patients with occult or prior hepatitis B infection (defined as positive total
             hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus
             (HBV) DNA is undetectable at the time of screening. These patients must be willing to
             undergo monthly DNA testing and appropriate antiviral therapy as indicated by
             institutional standard

          -  Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology
             testing)

             * Patients positive for HCV antibody are eligible only if polymerase chain reaction
             (PCR) is negative for HCV ribonucleic acid (RNA)

          -  History of uncontrolled human immunodeficiency virus (HIV)

             * Patients with known diagnosis of HIV must have undetectable viral load and be on
             anti-retroviral therapy

          -  Patients with a history of progressive multifocal leukoencephalopathy

          -  Pregnancy or lactation or intending to become pregnant during study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 30 days after last dose of polatuzumab or first administration of alternate therapy
Safety Issue:
Description:Will estimate the safety and tolerability of polatuzumab vedotin when added to dose-adjusted-etoposide, prednisone, vincristine (Oncovin), cyclophosphamide, doxorubicin-rituximab (DA-EPCH-R) chemoimmunotherapy.

Secondary Outcome Measures

Measure:The proportion of patients who are unable to complete 6 cycles of therapy for reasons other than disease progression
Time Frame:Up to 18 weeks
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Washington

Last Updated

January 14, 2020