Clinical Trials /

Brentuximab Vedotin With or Without Nivolumab in Treating Patients With Relapsed or Refractory CD30+ Lymphoma

NCT01703949

Description:

This phase II pilot trial studies how well brentuximab vedotin with or without nivolumab works in treating patients with CD30+ lymphoma that has come back after a period of improvement or does not respond to treatment. Biological therapies, such as brentuximab vedotin, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor cells to grow and spread. Giving brentuximab vedotin with or without nivolumab may work better in treating patients with CD30+ lymphoma.

Related Conditions:
  • Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Brentuximab Vedotin With or Without Nivolumab in Treating Patients With Relapsed or Refractory CD30+ Lymphoma
  • Official Title: A Pilot Study of Weekly Brentuximab Vedotin or Brentuximab Vedotin Plus Nivolumab Every 3 Weeks in Patients With CD30+ Malignancies Refractory to Every ≥ 3 Week Brentuximab Vedotin

Clinical Trial IDs

  • ORG STUDY ID: 7808
  • SECONDARY ID: NCI-2012-01696
  • SECONDARY ID: 7808
  • SECONDARY ID: P30CA015704
  • NCT ID: NCT01703949

Conditions

  • CD30-Positive Neoplastic Cells Present
  • Recurrent Hodgkin Lymphoma
  • Recurrent Non-Hodgkin Lymphoma
  • Refractory Hodgkin Lymphoma
  • Refractory Non-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-35Arm A (brentuximab vedotin)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoArm B (brentuximab vedotin, nivolumab)

Purpose

This phase II pilot trial studies how well brentuximab vedotin with or without nivolumab works in treating patients with CD30+ lymphoma that has come back after a period of improvement or does not respond to treatment. Biological therapies, such as brentuximab vedotin, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as nivolumab may interfere with the ability of tumor cells to grow and spread. Giving brentuximab vedotin with or without nivolumab may work better in treating patients with CD30+ lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To estimate the response rate following weekly brentuximab vedotin (1.2 mg/kg 3 of 4 weeks
      for up to four 28-day cycles) in patients with lack of response (< partial response [PR]) or
      progression following brentuximab vedotin and demonstrating persistent expression of CD30.
      (Arm A)

      II. To evaluate the response rate of combination brentuximab vedotin and nivolumab in
      patients with lack of response (< PR) or progression within 6 months following brentuximab
      vedotin. (Arm B)

      SECONDARY OBJECTIVES:

      I. To monitor clinical outcome following the study treatment regimen.

      II. To estimate the frequency of CD30 loss in patients following resistance to brentuximab
      vedotin.

      III. To describe the pattern of CD30 expression (membranous, cytoplasmic, Golgi) in
      comparison to the pre-brentuximab vedotin expression.

      IV. To semi-quantitatively estimate and compare the surface density of CD30 pre and post
      brentuximab vedotin as measured by flow cytometry.

      V. To correlate response with CD30 density as measured by flow cytometry.

      VI. To evaluate the tolerability of the weekly regimen in patients previously exposed to
      brentuximab vedotin.

      VII. To explore the tolerability of brentuximab vedotin and nivolumab in patients previously
      exposed to brentuximab vedotin in a 21-day cycle.

      OUTLINE:

      ARM A (CLOSED TO ACCRUAL): Patients receive brentuximab vedotin intravenously (IV) over 30
      minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the
      absence of disease progression or unacceptable toxicity.

      ARM B: Patients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60
      minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 3-5 weeks, every 3 months
      for 1 year, and then every 6 months for 4 years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (brentuximab vedotin)ExperimentalPatients receive brentuximab vedotin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
Arm B (brentuximab vedotin, nivolumab)ExperimentalPatients receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Relapsed or refractory CD30+ lymphoma that has either achieved < PR to brentuximab
             vedotin (minimum of 2 cycles), progressed while receiving brentuximab vedotin, or
             progressed within 6 months of the last dose of brentuximab vedotin

          -  Documented expression of CD30 on tumor cells

          -  Absolute neutrophil count (ANC) > 1,000/uL

          -  Platelets > 50,000/uL

          -  Serum creatinine < 1.5 mg/dL OR creatinine clearance > 60 mL/min

          -  Bilirubin < 1.5 x upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN

          -  Measurable disease by computed tomography (CT) or similar (e.g. magnetic resonance
             imaging [MRI]) criteria (> 1.5 cm)

          -  Resolution of all non-hematologic brentuximab vedotin-related adverse events (AEs) to
             < grade 2

          -  All patients must be informed of the investigational nature of this study and have
             given written consent in accordance with institutional and federal guidelines

          -  Patients must be anticipated to complete at least 2 cycles of chemotherapy on study

          -  Expected survival if untreated of > 90 days

        Exclusion Criteria:

          -  Prior transplant within 100 days

          -  Radioimmunotherapy within 12 weeks

          -  Known human immunodeficiency virus (HIV) or hepatitis B positivity or prior
             progressive multifocal leukoencephalopathy (PML)

          -  Active infection or other medical condition which would preclude treatment in the
             opinion of the principal investigator; this would include a corrected diffusing
             capacity of the lungs for carbon monoxide (DLCO) of < 60% predicted or symptomatic
             interstitial lung disease

          -  Eastern Cooperative Oncology Group (ECOG) performance status > 2

          -  Known active central nervous system (CNS) involvement

          -  Peripheral neuropathy > grade 1 if due to brentuximab vedotin or any peripheral
             neuropathy > grade 2

          -  Intolerance to brentuximab vedotin

          -  Concurrent use of other anti-cancer agents or experimental treatments

          -  No current or prior autoimmune disease with the exception of vitiligo and autoimmune
             alopecia (Arm B only)

          -  Pregnancy or breastfeeding; (females of childbearing potential must have a negative
             serum or urine beta human chorionic gonadotropin [beta-hCG] pregnancy test result
             within 7 days prior to the first dose of brentuximab vedotin; females with false
             positive results and documented verification that the patient is not pregnant are
             eligible for participation; females of non-childbearing potential are those who are
             postmenopausal greater than 1 year or who have had a bilateral tubal ligation or
             hysterectomy; females of childbearing potential and males who have partners of
             childbearing potential must agree to use 2 effective contraceptive methods during the
             study and for 6 months following the last dose of brentuximab vedotin or 8 months
             following the last dose of nivolumab, whichever is later)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate as measured by the Cheson 2007 criteria
Time Frame:Up to 5 weeks after completion of study treatment
Safety Issue:
Description:No formal statistical measures will be pre-specified. This protocol will be deemed a "success" if the absolute response rate in this group of patients is >= 20%.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

October 11, 2019