Clinical Trials /

Nivolumab in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma

NCT03075553

Description:

This phase II trial studies how well nivolumab works in treating patients with peripheral T-cell lymphoma that has come back after a period of improvement or that does not respond to treatment. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells.

Related Conditions:
  • Adult T-Cell Leukemia/Lymphoma
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Enteropathy-Associated T-Cell Lymphoma
  • Hepatosplenic T-Cell Lymphoma
  • Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
  • Mycosis Fungoides
  • NK-Cell Lymphoma, Unclassifiable
  • Nasal Type Extranodal NK/T-Cell Lymphoma
  • Peripheral T-Cell Lymphoma, NOS
  • Peripheral T-Cell Lymphoma, Unclassifiable
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma
  • Official Title: Phase 2 Single-Arm, Open-Label Study of Nivolumab in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)

Clinical Trial IDs

  • ORG STUDY ID: MC1681
  • SECONDARY ID: NCI-2017-00307
  • SECONDARY ID: MC1681
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT03075553

Conditions

  • Blastic Plasmacytoid Dendritic Cell Neoplasm
  • Hepatosplenic T-Cell Lymphoma
  • HTLV-1 Infection
  • NK-Cell Lymphoma, Unclassifiable
  • Primary Systemic Anaplastic Large Cell Lymphoma, ALK-Negative
  • Recurrent Adult T-Cell Leukemia/Lymphoma
  • Recurrent Anaplastic Large Cell Lymphoma
  • Recurrent Angioimmunoblastic T-cell Lymphoma
  • Recurrent Enteropathy-Associated T-Cell Lymphoma
  • Recurrent Mycosis Fungoides
  • Refractory Adult T-Cell Leukemia/Lymphoma
  • Refractory Anaplastic Large Cell Lymphoma
  • Refractory Angioimmunoblastic T-cell Lymphoma
  • Refractory Enteropathy-Associated T-Cell Lymphoma
  • Refractory Mycosis Fungoides
  • Refractory Nasal Type Extranodal NK/T-Cell Lymphoma
  • Refractory Peripheral T-Cell Lymphoma, Not Otherwise Specified

Interventions

DrugSynonymsArms
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoTreatment (nivolumab)

Purpose

This phase II trial studies how well nivolumab works in treating patients with peripheral T-cell lymphoma that has come back after a period of improvement or that does not respond to treatment. Monoclonal antibodies, such as nivolumab, may block cancer growth in different ways by targeting certain cells.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To assess the clinical benefit of nivolumab in T-cell lymphomas, as measured by objective
      response rate (ORR) within 12 cycles according to the Lugano Classification Response Criteria
      (2014).

      SECONDARY OBJECTIVES:

      I. To assess safety and tolerability of the regimen in this patient population. II. To assess
      progression-free survival (PFS). III. To assess duration of response (DOR). IV. To assess
      overall survival (OS).

      TERTIARY OBJECTIVES:

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

      II. To evaluate intratumoral biomarkers- intratumoral cell populations and distribution,
      genetic variability, mutational burden and T-cell activation will be evaluated to identify
      potential biomarkers that correlate with response to therapy.

      III. To assess the potential association between PD-L1/PD-1/PD-L2 expression on tumor and
      T-cells and/or PD-L1 soluble levels in plasma with clinical efficacy of PD-1 blockade.

      OUTLINE:

      Patients receive nivolumab intravenously (IV) over 60 minutes on day 1. Treatment repeats
      every 14 days for up to 8 courses in the absence of disease progression or unacceptable
      toxicity. Patients achieving stable disease, complete response, or partial response receive
      nivolumab IV over 60 minutes on day 1 of course 9. Treatment repeats every 28 days for up to
      24 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 35 days, 100-120 days,
      230-250 days, and 330-390 days.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (nivolumab)ExperimentalPatients receive nivolumab IV over 60 minutes on day 1. Treatment repeats every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease, complete response, or partial response receive nivolumab IV over 60 minutes on day 1 of course 9. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Relapsed or refractory T-cell lymphoma (TCL) biopsy-proven =< 6 months prior to
                 registration, including the following subtypes:
    
                   -  Peripheral T-cell lymphoma, not otherwise specified
    
                   -  Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK) negative,
                      primary systemic type
    
                   -  Angioimmunoblastic T-cell lymphoma
    
                   -  Extranodal natural killer (NK)/T-cell lymphoma, nasal type
    
                   -  Adult T-cell lymphoma/leukemia (human T-lymphotropic virus 1 [HTLV1]+)
    
                   -  Blastic NK-cell lymphoma
    
                   -  Enteropathy-associated T-cell lymphoma
    
                   -  Hepatosplenic gamma delta T-cell lymphoma
    
                   -  Transformed mycosis fungoides
    
                   -  T/NK-cell lymphoma, unclassifiable
    
              -  Measurable disease: subjects must have at least one lesion that is > 15mm (1.5 cm) in
                 the longest diameter on cross-sectional imaging and measureable in two perpendicular
                 dimensions per computed tomography (spiral CT) or magnetic resonance imaging (MRI)
    
              -  After failure of allogeneic stem cell transplant (ASCT) or after failure of frontline
                 therapy in subjects who declined or are not ASCT candidates
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
    
              -  White blood cell (WBC) >= 3000/mm^3
    
              -  Absolute neutrophil count (ANC) >= 1500/mm^3
    
              -  Platelet count >= 100,000/mm^3
    
              -  Hemoglobin > 9.0 g/dL
    
              -  Total bilirubin =< 1.5 x upper limit of normal (ULN) unless elevation due to Gilbert's
                 Syndrome
    
              -  Aspartate transaminase (AST) =< 2.5 x ULN
    
              -  Creatinine =< 2.0 mg/dL
    
              -  Calculated creatinine clearance must be >= 45 ml/min using the Cockcroft-Gault formula
    
              -  Negative serum or urine pregnancy test done =< 7 days prior to registration, for
                 persons of childbearing potential only Note: Persons of child-bearing potential
                 (POCBP) must use appropriate method(s) of contraception; POCBP 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 POCBP must use any contraceptive method with a failure rate of
                 less than 1% per year; men receiving nivolumab and who are sexually active with POCBP
                 will be instructed to adhere to contraception for a period of 31 weeks after the last
                 dose of investigational product; persons who are not of childbearing potential (ie,
                 who are postmenopausal or surgically sterile) as well as azoospermic men do not
                 require contraception; should a person become pregnant or suspect being pregnant while
                 participating in this study, the person should inform the treating physician
                 immediately
    
              -  Provide written informed consent
    
              -  Willing to return to enrolling institution for follow-up during the Active Monitoring
                 phase of the study
    
              -  Willing to provide tissue and blood samples for correlative research purposes
    
            Exclusion Criteria:
    
              -  All primary cutaneous T-cell lymphomas
    
              -  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
    
              -  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 are permitted; > 10 mg daily prednisone equivalents are
                 permitted only in adrenal insufficiency in the absence of active autoimmune disease
    
              -  Prohibited treatments and or therapies
    
                   -  Autologous stem cell transplant (ASCT) =< 12 weeks prior to first dose of the
                      study drug
    
                   -  Prior treatments (window prior to registration):
    
                        -  Chemotherapy =< 2 weeks
    
                        -  Nitrosureas =< 6 weeks
    
                        -  Therapeutic anticancer antibodies =< 4 weeks
    
                        -  Radio- or toxin immunoconjugates =< 10 weeks
    
                        -  Radiation therapy =< 3 weeks
    
                        -  Or major surgery =< 2 weeks
    
                   -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody,
                      or any other antibody or drug specifically targeting T-cell costimulation or
                      immune checkpoint pathways
    
                        -  Prior allogeneic stem cell transplant (SCT)
    
                        -  Chest radiation =< 24 weeks prior to registration
    
              -  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, active hepatitis B virus surface antigen
                 (HBV sAg+), active hepatitis C (if Ab+ then PCR+) indicating acute or chronic
                 infection
    
              -  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
    
              -  Other active malignancy =< 3 years prior to registration EXCEPTIONS: non-melanotic
                 skin cancer or carcinoma-in-situ of the cervix NOTE: if there is a history of prior
                 malignancy, they must not be receiving other specific treatment for their cancer
    
              -  Active central nervous system (CNS) involvement or leptomeningeal involvement
    
              -  History of pancreatitis
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Proportion of complete or partial responses assessed according to the revised Lugano Classification Response criteria
    Time Frame:Up to 390 days
    Safety Issue:
    Description:The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients.

    Secondary Outcome Measures

    Measure:Duration of Complete Response (DOR)
    Time Frame:Up to 390 days
    Safety Issue:
    Description:The distribution of duration of complete response will be estimated using the method of Kaplan-Meier.
    Measure:Incidence of adverse events
    Time Frame:Up to 390 days
    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.
    Measure:Incidence of adverse events
    Time Frame:Up to 390 days
    Safety Issue:
    Description:The relationship of the adverse event(s) to the study treatment will be taken into consideration.
    Measure:Overall Survival (OS)
    Time Frame:The time from registration to death due to any cause, assessed up to 2 years
    Safety Issue:
    Description:The distribution of survival time will be estimated using the method of Kaplan-Meier.
    Measure:Progression-Free Survival (PFS)
    Time Frame:The time from registration to relapse 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. In addition, the progression-free survival rate will be reported.
    Measure:Progression-Free Survival (PFS)
    Time Frame:The time from registration to relapse or death due to any cause, assessed up to 5 years
    Safety Issue:
    Description:The progression-free survival rate will be reported.
    Measure:Response rates
    Time Frame:Up to 390 days
    Safety Issue:
    Description:Will be estimated using complete metabolic response divided by the total number of evaluable patients.
    Measure:Response rates
    Time Frame:Up to 390 days
    Safety Issue:
    Description:Will be estimated using partial metabolic response divided by the total number of evaluable patients.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Mayo Clinic

    Last Updated

    May 22, 2017