Clinical Trials /

Feasibility Study of Induction and Maintenance Avelumab Plus R-CHOP in Patients With Diffuse DLBCL: The AvR-CHOP Study

NCT03244176

Description:

To evaluate the feasibility of adding induction and maintenance Avelumab to the standard combination of R-CHOP in patients with stage II, III and IV diffuse large B cell lymphoma (DLBCL)

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

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Feasibility Study of Induction and Maintenance Avelumab Plus R-CHOP in Patients With Diffuse DLBCL: The AvR-CHOP Study
  • Official Title: Feasibility Study of Induction and Maintenance Avelumab Plus R-CHOP in Patients With Diffuse Large B Cell Lymphoma (DLBCL): The AvR-CHOP Study

Clinical Trial IDs

  • ORG STUDY ID: MS100070-0068
  • NCT ID: NCT03244176

Conditions

  • Lymphomas Non-Hodgkin's B-Cell

Interventions

DrugSynonymsArms
AvelumabMSB0010718COpen-label

Purpose

To evaluate the feasibility of adding induction and maintenance Avelumab to the standard combination of R-CHOP in patients with stage II, III and IV diffuse large B cell lymphoma (DLBCL)

Detailed Description

      The rationale and primary objective is to evaluate the feasibility of adding induction and
      maintenance Avelumab into the standard Rituximab, Cyclophosphamide, Doxyrubicin, Vincristine
      and Prednisolone (RCHOP) regimen in order to examine the effect of programmed death-ligand
      1(PDL1) inhibition in patients with stage II, III and IV DLBCL.

      Primary endpoint:

      • Immune related toxicity which requires discontinuation of Avelumab.

      Secondary endpoints:

        -  Response rates (according to the Lugano classification for Response Criteria for
           NonHodgkin Lymphoma);

        -  Failure free survival;

        -  Overall survival;

        -  Overall toxicity of treatment (according to CTCAE v 4.0).

      Methodology:

      All patients (n=28) will receive Avelumab and rituximab 2 weekly for 2 cycles, then RCHOP
      chemotherapy 3 weekly for 6 cycles then Avelumab 2 weekly for 6 cycles.

      The sequential treatment schedule has been designed for several reasons: concurrent Avelumab
      and RCHOP might result in reduced efficacy of Avelumab owing to the high dose prednisolone
      component of RCHOP; immune related toxicities of Avelumab given concurrently with RCHOP might
      result in chemotherapy dose delays and reduced chemotherapy efficacy; the Avelumab plus
      rituximab prephase will allow for the preliminary assessment of nonchemotherapy agents
      Avelumab plus rituximab in treatment naïve patients.

      Assessments:

        -  Patients will be reviewed at baseline and prior to each cycle of treatment for toxicity

        -  Positron emission tomography-computed tomography (PET/CT) will be performed at baseline,
           after induction phase, after cycle 2 RCHOP, at end of Avelumab (Av) RCHOP and at end of
           maintenance phase Avelumab.

        -  Following completion of treatment, patients will be followed up for a total of 5 years
           (at 3,6,9,12,18,24,36,48 and 60 months posttreatment). No formal routine imaging will be
           performed during follow up. In patients with relapse, follow up only for survival will
           be every 3 months.
    

Trial Arms

NameTypeDescriptionInterventions
Open-labelOtherAvelumab - Single-arm open label study
  • Avelumab

Eligibility Criteria

        Inclusion Criteria:

          1. Male or Female subjects aged 18 years.

          2. Histologically proven CD20-positive diffuse large B cell non-Hodgkin lymphoma (DLBCL)
             according to the current World Health Organization classification including all
             morphological variants.

          3. No previous treatment for lymphoma including chemotherapy, radiotherapy or other
             investigational drug.

          4. Stage II, III and IV disease (Ann Arbor criteria) (must be able to undergo PET/CT
             imaging for staging purposes.)

          5. Eastern Collaborative Oncology Group performance status 0, or 1, unless attributable
             to lymphoma in which case patients of performance status 2 are also eligible.

          6. Adequate bone marrow function with platelets > 100x109/l; neutrophils > 1.5x109/l at
             the time of study entry unless attributed to bone marrow infiltration by lymphoma.

          7. Adequate renal function defined by an estimated creatinine clearance ≥ 30 mL/min
             according to the Cockcroft-Gault formula (or local institutional standard method)

          8. Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit
             of normal (ULN) range and aspartate aminotransferase (AST) and alanine
             aminotransferase (ALT) levels ≤ 2.5 × upper limit of institutional normal range unless
             attributed to lymphoma.

          9. Patients must have an acceptable left ventricular ejection fraction (LVEF) i.e. within
             the local normal range for multigated acquisition scan (MUGA) or ≥ 45% on
             echocardiogram

         10. No concurrent uncontrolled medical condition as determined by the investigator.

         11. Life expectancy > 3 months.

         12. Negative blood pregnancy test at screening for women of childbearing potential.
             Effective contraception for both male and female subjects if the risk of conception
             exists.

         13. Signed written informed consent before any trial-related procedure is undertaken that
             is not part of the standard patient management.

        Exclusion Criteria:

          1. T-cell lymphoma, transformed follicular lymphoma, grade 3B Follicular lymphoma.

          2. Previous history of treated or non-treated indolent lymphoma. However, patients not
             previously diagnosed with an indolent lymphoma, who have diffuse large B-cell lymphoma
             with some small cell infiltration in bone marrow or lymph node may be included after
             consultation with the sponsor.

          3. Central nervous system, meningeal or spinal cord involvement by lymphoma.

          4. Prior therapy with any antibody or drug targeting T-cell coregulatory proteins (immune
             checkpoints) such as PD-1, PD-L1, or cytotoxic T-lymphocyte antigen-4 (CTLA-4).

          5. Patients with active autoimmune disease that might deteriorate when receiving an
             immunostimulatory agent:

        i) Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not
        requiring immunosuppressive treatment are eligible ii) Subjects requiring hormone
        replacement with corticosteroids are eligible if the steroids are administered only for the
        purpose of hormonal replacement and at doses ≤ 10 mg or 10 mg equivalent prednisone per day
        iii) Administration of steroids through a route known to result in a minimal systemic
        exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable.

        f) Subjects with a condition requiring systemic treatment with either corticosteroids (> 15
        mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of
        study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 15
        mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

        g) Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTCAE v
        4.03), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of
        partially controlled asthma) h) Past history of interstitial lung disease. i) Prior organ
        transplantation, including allogeneic stem-cell transplantation j) Prior malignancy active
        within the previous 3 years except for locally curable cancers that have been apparently
        cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma
        in situ of the prostate, cervix, or breast.

        k) Neurological contra-indication to vincristine (e.g. pre-existing diabetic neuropathy
        >grade 1) l) Major surgery for any reason, except diagnostic biopsy, within 4 weeks of
        enrolment and/or if the subject has not fully recovered from the surgery within 4 weeks of
        enrolment m) Any other serious active disease, including but not limited to; i) pregnancy
        or lactation, ii) clinically significant (i.e., active) cardiovascular disease: cerebral
        vascular accident/stroke (< 6 months prior to enrolment), myocardial infarction (< 6 months
        prior to enrolment), unstable angina pectoris, congestive heart failure (New York Heart
        Association Classification Class ≥ II), or serious cardiac arrhythmia requiring medication
        (including QTc prolongation of > 470 ms and/or pacemaker) or prior diagnosis of congenital
        long QT syndrome.

        iii) or, uncontrolled active infection, iv) or, uncontrolled diabetes (e.g., hemoglobin A1c
        ≥ 8%) n) Known history of testing positive for human immunodeficiency virus (HIV) or known
        acquired immunodeficiency syndrome (AIDS), Hepatitis B virus (HBV) or hepatitis C virus
        (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody
        screening test positive) o) Medical or psychiatric conditions that compromise the patient's
        ability to give informed consent.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Immune-related toxicity
Time Frame:12 months
Safety Issue:
Description:Immune-related toxicity which requires discontinuation of Avelumab

Secondary Outcome Measures

Measure:Response Rate
Time Frame:5 years
Safety Issue:
Description:Response Rate to Avelumab + RCHOP according to the Lugano classification for Response Criteria for Non-Hodgkin Lymphoma
Measure:Failure Free Survival
Time Frame:5 years
Safety Issue:
Description:Duration of survival without additional systemic therapy, relapse or non-relapse mortality
Measure:Overall Survival
Time Frame:5 years
Safety Issue:
Description:Duration of patient survival
Measure:Overall Toxicity of Treatment
Time Frame:12 months
Safety Issue:
Description:Overall toxicity as assessed by CTCAE v4.0

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Austin Health

Trial Keywords

  • DLBCL

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