Clinical Trials /

Nivolumab Maintenance Therapy After Autologous Stem Cell Transplant in Hodgkin Lymphoma Pts at Relapse/Progression Risk

NCT03436862

Description:

This is a Phase II single-arm open-label study of nivolumab as maintenance therapy after autologous stem cell transplantation in patients with Hodgkin lymphoma at risk of relapse or progression.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab Maintenance Therapy After Autologous Stem Cell Transplant in Hodgkin Lymphoma Pts at Relapse/Progression Risk
  • Official Title: A Phase II Single Arm Study of Nivolumab as Maintenance Therapy After Autologous Stem Cell Transplantation in Patients With Hodgkin Lymphoma at Risk of Relapse or Progression

Clinical Trial IDs

  • ORG STUDY ID: SCRI BMT 24
  • NCT ID: NCT03436862

Conditions

  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab

Purpose

This is a Phase II single-arm open-label study of nivolumab as maintenance therapy after autologous stem cell transplantation in patients with Hodgkin lymphoma at risk of relapse or progression.

Detailed Description

      The primary objective of this study is to evaluate safety and tolerability of nivolumab as
      maintenance therapy early after autologous stem cell transplant in patients with Hodgkin's
      Lymphoma (HL).

      Eligible patients will receive nivolumab (240 mg IV) every 2 weeks (± 2 days as long as
      interval between doses is 12-16 days) starting 45-120 post-transplant for up to a maximum of
      6 months of treatment. Response to treatment will be assessed 6 months and 1 year
      post-transplant using Recommendations for Initial Evaluation, Staging, and Response
      Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.
    

Trial Arms

NameTypeDescriptionInterventions
NivolumabExperimentalPatients will receive Nivolumab 240 mg by intravenous infusion (IV) starting Day 45-120 post-transplant (±10 days) every 2 weeks for up to a maximum of 6 months of treatment.
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients 18 years of age and older with Hodgkin Lymphoma who have received auto-HSCT
             in the previous 45-120 days.

          -  Complete response (CR), partial response (PR) or stable disease (SD) to salvage
             therapy prior to ASCT.

          -  High risk of residual HL post-ASCT, as determined by 1 of the following:

               -  Positive positron emission tomography (PET) scan defined by the Deauville scale
                  3-4 and within 2 months of start of high dose chemotherapy prior to ASCT

               -  Refractory to frontline therapy

               -  Relapse <12 months after frontline therapy

               -  Relapse ≥12 months after frontline therapy with extra-nodal disease

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 - 1.

          -  Adequate hematologic function defined as all of the following:

               -  Absolute neutrophil count (ANC) ≥1000/μL

               -  Hemoglobin (Hgb) ≥8 g/dL (transfusions to reach this point are not permitted)

               -  Platelets ≥50,000/μL (transfusion is not permitted)

          -  Adequate liver function defined as all of the following:

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x the
                  upper limit of normal (ULN)

               -  Total bilirubin ≤1.5 x ULN (unless the patient has Grade 1 bilirubin elevation
                  due to Gilbert's disease or a similar syndrome involving slow conjugation of
                  bilirubin)

          -  Adequate renal function defined as serum creatinine ≤1.5 mg/dL (133 μmol/L).

          -  Females of childbearing potential must have a negative serum or urine pregnancy test
             result within 72 hours prior to the first dose of nivolumab and must agree to follow
             instructions for method(s) of contraception for the duration of treatment with
             nivolumab and for 7 months following their last dose of study drug. Females of
             non-childbearing potential are those who are postmenopausal greater than 1 year or who
             have had a bilateral tubal ligation or hysterectomy.

          -  Male patients with female partners of childbearing potential and women patients of
             childbearing potential are required to use two forms of acceptable contraception,
             including one barrier method, during their participation in the study and for 7 months
             following last dose of study drug. Male patients must also refrain from donating sperm
             during their participation in the study and for 7 months following last dose of study
             drug.

        Exclusion Criteria:

          -  Patients that have received an allogenic transplant.

          -  Post-ASCT or current therapy with other anti-neoplastic or investigational agents.

          -  Best clinical response of progressive disease prior to ASCT.

          -  Patients with any autoimmune disease or a history of autoimmune disease. Patients with
             vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune
             condition only requiring hormone replacement, psoriasis not requiring systemic
             treatment, or conditions not expected to recur in the absence of an external trigger
             are permitted to enroll.

          -  Any condition requiring systemic treatment with corticosteroids (> 10 mg daily
             prednisone equivalents) or other immunosuppressive medications within 14 days prior to
             first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10
             mg daily prednisone equivalents are permitted in the absence of active autoimmune
             disease.

          -  Use of a study drug ≤ 21 days or 5 half-lives (whichever is shorter) prior to the
             first dose of nivolumab. For study drugs for which 5 half-lives is ≤21 days, a minimum
             of 10 days between termination of the study drug and administration of nivolumab is
             required.

          -  Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89)
             administered ≤28 days or limited field radiation for palliation ≤7 days prior to
             starting study drug or has not recovered from side effects of such therapy.

          -  Major surgical procedures ≤28 days of beginning study drug, or minor surgical
             procedures ≤7 days. No waiting required following port-a-cath placement.

          -  Previously untreated brain metastases. Patients who have received radiation or surgery
             for brain metastases are eligible if therapy was completed at least 2 weeks prior to
             study entry and there is no evidence of central nervous system disease progression,
             mild neurologic symptoms, and no requirement for chronic corticosteroid therapy.

          -  Pregnant or lactating

          -  Acute or chronic liver, renal, or pancreatic disease.

          -  Uncontrolled diabetes mellitus. Patients with Type II diabetes are eligible if they
             require only oral hypoglycemic agents.

          -  Any of the following cardiac diseases currently or within the last 6 months:

               -  Left Ventricular Ejection Fraction (LVEF) <45% as determined by Multiple Gated
                  Acquisition (MUGA) scan or echocardiogram (ECHO)

               -  QTc interval >480 ms on screening electrocardiogram (ECG)

               -  Unstable angina pectoris

               -  Congestive heart failure (New York Heart Association (NYHA) ≥ Grade 2

               -  Acute myocardial infarction

               -  Conduction abnormality not controlled with pacemaker or medication

               -  Significant ventricular or supraventricular arrhythmias (patients with chronic
                  rate- controlled atrial fibrillation in the absence of other cardiac
                  abnormalities are eligible)

               -  Valvular disease with significant compromise in cardiac function

          -  Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] >180 mmHg or
             diastolic blood pressure (DBP) >100 mmHg) (patients with values above these levels
             must have their blood pressure (BP) controlled with medication prior to starting
             treatment).

          -  Serious active infection at the time of treatment, or another serious underlying
             medical condition that would impair the ability of the patient to receive protocol
             treatment.

          -  Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C. Testing
             at baseline is not required.

          -  Presence of other active cancers, or history of treatment for invasive cancer ≤5
             years. Patients with Stage I cancer who have received definitive local treatment and
             are considered unlikely to recur are eligible. All patients with previously treated in
             situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of
             non-melanoma skin cancer.

          -  Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) as a measure of safety
Time Frame:Up to 6 months
Safety Issue:
Description:The reported incidence of AEs and SAEs with an onset on or after the initiation of therapy will be graded according to National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE).

Secondary Outcome Measures

Measure:12 month progression-free survival (PFS)
Time Frame:1 year post-transplant
Safety Issue:
Description:The number of patients who are progression-free at 12 months post-transplant.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:SCRI Development Innovations, LLC

Trial Keywords

  • Nivolumab
  • Autologous Stem Cell Transplant
  • Blood cancers

Last Updated

October 3, 2019