Clinical Trials /

Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodgkin Lymphoma

NCT02758717

Description:

This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Biological therapies, such as brentuximab vedotin, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Nivolumab and brentuximab vedotin may work better in treating older patients with untreated Hodgkin lymphoma.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab and Brentuximab Vedotin in Treating Older Patients With Untreated Hodgkin Lymphoma
  • Official Title: Phase II, Multi-Center Trial of Nivolumab and Brentuximab Vedotin in Patients With Untreated Hodgkin Lymphoma Over the Age of 60 Years or Unable to Receive Standard Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: RU051505I
  • SECONDARY ID: NCI-2016-00468
  • SECONDARY ID: RU051505I
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02758717

Conditions

  • Ann Arbor Stage IB Hodgkin Lymphoma
  • Ann Arbor Stage II Hodgkin Lymphoma
  • Ann Arbor Stage IIA Hodgkin Lymphoma
  • Ann Arbor Stage IIB Hodgkin Lymphoma
  • Ann Arbor Stage III Hodgkin Lymphoma
  • Ann Arbor Stage IIIA Hodgkin Lymphoma
  • Ann Arbor Stage IIIB Hodgkin Lymphoma
  • Ann Arbor Stage IV Hodgkin Lymphoma
  • Ann Arbor Stage IVA Hodgkin Lymphoma
  • Ann Arbor Stage IVB Hodgkin Lymphoma
  • Classic Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Brentuximab VedotinADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35, Anti-CD30 Monoclonal Antibody-Monomethylauristatin E SGN-35, cAC10-vcMMAE, SGN-35Treatment (brentuximab vedotin, nivolumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (brentuximab vedotin, nivolumab)

Purpose

This phase II trial studies how well nivolumab and brentuximab vedotin work in treating older patients with untreated Hodgkin lymphoma. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as brentuximab vedotin, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Nivolumab and brentuximab vedotin may work better in treating older patients with untreated Hodgkin lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the efficacy based on overall metabolic response rate (partial metabolic
      response [PMR] + complete metabolic remission [CMR]) of brentuximab vedotin/nivolumab in
      previously untreated Hodgkin lymphoma patients 60 years of age or older, or those considered
      unsuitable for standard chemotherapy because of a low cardiac ejection fraction (< 50%) or
      impaired pulmonary or renal function.

      SECONDARY OBJECTIVES:

      I. The complete metabolic response (CMR) rate. II. Safety and tolerability of the regimen in
      this patient population. III. Duration of response (DOR). IV. Progression-free survival
      (PFS). V. Overall survival (OS).

      TERTIARY OBJECTIVES:

      I. T-cell/cytokine - peripheral blood specimens will be used to assess T-cell activation and
      cytokine up regulation as measures of treatment effect.

      II. Biomarkers - intratumoral cell populations, genetic variability, serum cytokines and
      T-cell activation will be evaluated to identify potential biomarkers that correlate with
      response to therapy.

      OUTLINE:

      Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab IV over
      60 minutes on day 1. Treatment repeats every 21 days for 7 courses and 6-8 weeks in course 8
      in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 30 days for 90 days,
      every 90 days for 2.5 years, and then every 6 months until 5 years from registration.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (brentuximab vedotin, nivolumab)ExperimentalPatients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 60 minutes on day 1. Treatment repeats every 21 days for 7 courses and 6-8 weeks in course 8 in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Classical Hodgkin lymphoma determined by local hematopathology review

          -  One of the following:

               -  Age >= 60 years

               -  Age < 60 years but unsuitable for standard chemotherapy because of a cardiac
                  ejection fraction of < 50%, a pulmonary diffusion capacity < 80%, or a creatinine
                  clearance >= 30 and < 60 mL/min, or refused standard chemotherapy despite efforts
                  to convince them otherwise

          -  Requirement for systemic chemotherapy: all stages except IA (not bulky disease), if
             involved field is considered radiotherapy (RT) curative

          -  Previously untreated with either chemotherapy, radiation therapy or either brentuximab
             vedotin or nivolumab, or another check point inhibitor

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2

          -  Absolute neutrophil count (ANC) >= 1500/mm^3, unless secondary to bone marrow
             involvement; obtained =< 7 days prior to registration

          -  Leukocytes >= 3,000/mm^3, obtained =< 7 days prior to registration

          -  Platelet count >= 100,000/mm^3, obtained =< 7 days prior to registration

          -  Hemoglobin > 9.0 g/dL ? unless determined by treating physician to be disease related,
             obtained =< 7 days prior to registration

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN), obtained =< 7 days prior to
             registration

          -  Aspartate aminotransferase (aspartate transaminase [AST]) =< 2.5 x ULN, obtained =< 7
             days prior to registration

          -  Alanine aminotransferase (alanine transaminase [ALT]) =< 2.5 x ULN, obtained =< 7 days
             prior to registration

          -  Creatinine =< 2.0 mg/dL, obtained =< 7 days prior to registration

          -  Amylase and/or lipase =< 1.5 x ULN, obtained =< 7 days prior to registration

          -  Women of childbearing potential must have a negative serum or urine pregnancy test
             (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin
             [HCG]) within 24 hours prior to registration

               -  Note: women of child-bearing potential (WOCBP) must use appropriate method(s) of
                  contraception; WOCBP should use an adequate method to avoid pregnancy for 23
                  weeks (30 days plus the time required for nivolumab to undergo five half-lives)
                  after the last dose of investigational drug; men who are sexually active with
                  WOCBP must use any contraceptive method with a failure rate of less than 1% per
                  year; men receiving nivolumab and who are sexually active with WOCBP will be
                  instructed to adhere to contraception for a period of 31 weeks after the last
                  dose of investigational product; women who are not of childbearing potential
                  (i.e., who are postmenopausal or surgically sterile) as well as azoospermic men
                  do not require contraception; should a woman become pregnant or suspect she is
                  pregnant while participating in this study, she should inform her treating
                  physician immediately

          -  Willing to return to enrolling institution for follow-up (during the active monitoring
             phase of the study)

               -  Note: during the active monitoring phase of a study (i.e., active treatment and
                  observation), participants must be willing to return to the consenting
                  institution for follow-up

          -  Ability to understand and willingness to sign an informed written consent

          -  Provide blood and tissue samples for mandatory correlative research purposes

        Exclusion Criteria:

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment
             of the investigator, would make the patient inappropriate for entry into this study or
             interfere significantly with the proper assessment of safety and toxicity of the
             prescribed regimens

          -  Active, known or suspected autoimmune disease; note: subjects are permitted to enroll
             if they have 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

          -  Use of systemic treatment with either corticosteroids (> 10 mg daily prednisone
             equivalents) or other immunosuppressive medications =< 14 days of registration; Note:
             Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone
             equivalents are permitted in the absence of active autoimmune disease

          -  Immunocompromised patients, patients with known history of testing positive for human
             immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) and
             currently receiving antiretroviral therapy, patients with a prior history of known or
             suspected autoimmune disease, active hepatitis B virus surface antigen (HBV sAg+),
             active Hepatitis C (if antibody [Ab]+ then polymerase chain reaction [PCR]+)
             indicating acute or chronic infection, and/or history of interstitial lung disease

          -  Allergy to brentuximab vedotin and/or nivolumab

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Receiving any other investigational agent which would be considered as a treatment for
             the primary neoplasm

          -  Have had prior chemotherapy or radiotherapy for Hodgkin lymphoma

          -  Have received either of the study drugs

          -  < 60 years who are considered candidates for standard chemotherapy

          -  >= grade 2 peripheral neuropathy

          -  Other active malignancy =< 2 years prior to registration, unless treated with curative
             intent; EXCEPTIONS: non-melanotic skin cancer or carcinoma-in-situ of the cervix;
             NOTE: if there is a history or prior malignancy, they must not be receiving other
             specific treatment for their cancer

          -  Active central nervous system (CNS) involvement or leptomeningeal metastases
             involvement

          -  Known history of pancreatitis
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall metabolic response
Time Frame:Up to end of course 8
Safety Issue:
Description:The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

Secondary Outcome Measures

Measure:Complete metabolic response rate estimated by the total number of complete metabolic responses (CMR) divided by the total number of evaluable patients
Time Frame:Up to 5 years
Safety Issue:
Description:Exact binomial 95% confidence intervals for the true complete metabolic response rate will be calculated.
Measure:Duration of response
Time Frame:From date at which the patient?s objective status is first noted to be a CMR or PMR to the earliest date progression (progressive metabolic disease [PMD] or progressive disease [PD]) is documented, assessed up to 5 years
Safety Issue:
Description:The distribution of duration of response will be estimated using the method of Kaplan-Meier.
Measure:Progression-free survival
Time Frame:Time from registration to the earliest date of documentation of disease progression (PMD or PD) or death due to any cause, assessed up to 5 years
Safety Issue:
Description:The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.
Measure:Overall survival
Time Frame:Time from registration to death due to any cause, assessed up to 5 years
Safety Issue:
Description:The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Measure:Incidence of adverse events graded by Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 5 years
Safety Issue:
Description:The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Academic and Community Cancer Research United

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