Clinical Trials /

Brentuximab Vedotin and Nivolumab in Treating Patients With Early Stage Classic Hodgkin Lymphoma

NCT03712202

Description:

This phase II trial studies how well brentuximab vedotin and nivolumab work in treating patients with stage I-II classic Hodgkin lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. 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.

Related Conditions:
  • Classical Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Brentuximab Vedotin and Nivolumab in Treating Patients With Early Stage Classic Hodgkin Lymphoma
  • Official Title: A Phase 2 Front-Line PET/CT-2 Response-Adapted Brentuximab Vedotin and Nivolumab Incorporated and Radiation-Free Management of Early Stage Classical Hodgkin Lymphoma (cHL)

Clinical Trial IDs

  • ORG STUDY ID: 18157
  • SECONDARY ID: NCI-2018-01592
  • SECONDARY ID: 18157
  • NCT ID: NCT03712202

Conditions

  • Ann Arbor Stage I Hodgkin Lymphoma
  • Ann Arbor Stage I Lymphocyte-Depleted Classic Hodgkin Lymphoma
  • Ann Arbor Stage I Mixed Cellularity Classic Hodgkin Lymphoma
  • Ann Arbor Stage I Nodular Sclerosis Classic Hodgkin Lymphoma
  • Ann Arbor Stage IA Hodgkin Lymphoma
  • Ann Arbor Stage IB Hodgkin Lymphoma
  • Ann Arbor Stage II Hodgkin Lymphoma
  • Ann Arbor Stage II Lymphocyte-Depleted Classic Hodgkin Lymphoma
  • Ann Arbor Stage II Mixed Cellularity Classic Hodgkin Lymphoma
  • Ann Arbor Stage II Nodular Sclerosis Classic Hodgkin Lymphoma
  • Ann Arbor Stage IIA Hodgkin Lymphoma
  • Ann Arbor Stage IIB Hodgkin Lymphoma
  • Classic Hodgkin Lymphoma
  • Lymphocyte-Rich Classic Hodgkin Lymphoma

Interventions

DrugSynonymsArms
BleomycinBLEO, BLMGroup I Arm B (ABVD, nivolumab)
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-35Group I Arm A (brentuximab vedotin, nivolumab)
Dacarbazine4-(Dimethyltriazeno)imidazole-5-carboxamide, 5-(Dimethyltriazeno)imidazole-4-carboxamide, Asercit, Biocarbazine, Dacarbazina, Dacarbazina Almirall, Dacarbazine - DTIC, Dacatic, Dakarbazin, Deticene, Detimedac, DIC, Dimethyl (triazeno) imidazolecarboxamide, Dimethyl Triazeno Imidazol Carboxamide, Dimethyl Triazeno Imidazole Carboxamide, dimethyl-triazeno-imidazole carboxamide, Dimethyl-triazeno-imidazole-carboximide, DTIC, DTIC-Dome, Fauldetic, Imidazole Carboxamide, Imidazole Carboxamide Dimethyltriazeno, WR-139007Group I Arm B (ABVD, nivolumab)
DoxorubicinAdriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, HydroxyldaunorubicinGroup I Arm B (ABVD, nivolumab)
NivolumabBMS-936558, MDX-1106, NIVO, ONO-4538, OpdivoGroup I Arm A (brentuximab vedotin, nivolumab)
VinblastineVincaleucoblastine, VLBGroup I Arm B (ABVD, nivolumab)

Purpose

This phase II trial studies how well brentuximab vedotin and nivolumab work in treating patients with stage I-II classic Hodgkin lymphoma. Brentuximab vedotin is a monoclonal antibody, brentuximab, linked to a toxic agent called vedotin. Brentuximab attaches to CD30 positive cancer cells in a targeted way and delivers vedotin to kill them. 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.

Detailed Description

      PRIMARY OBJECTIVE:

      I. Determine the 18‐month progression free survival (PFS) for each arm of therapy stratified
      by positron emission tomography (PET)/computed tomography (CT)‐2 response.

      SECONDARY OBJECTIVES:

      I. Assess safety, tolerability, and quality of life (QOL) for each arm of therapy.

      II. Measure PET/CT‐2 negativity rate after 2 lead‐in cycles of standard of care doxorubicin,
      bleomycin, vinblastine, dacarbazine (ABVD).

      III. Evaluate the 3‐year PFS and overall survival (OS) for each arm of treatment.

      EXPLORATORY OBJECTIVES:

      I. Evaluate if a baseline antitumor immune response, as assessed by a Nanostring gene panel,
      correlates with PFS.

      II. Evaluate if minimal residual disease (MRD) status, as monitored by cancer personalized
      profiling by deep sequencing (CAPP‐Seq) of circulating tumor (ct) deoxyribonucleic acid
      (DNA), can be correlated with PFS.

      OUTLINE: Patients are assigned to 1 of 2 groups based on their PET/CT-2 scans.

      GROUP I (PET/CT-2 NEGATIVE): Patients without bulky disease are randomized to either Arm A or
      B and patients with bulky disease are assigned to Arm B.

      ARM A: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes and nivolumab
      IV over 60 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the
      absence of disease progression or unacceptable toxicity.

      ARM B: Patients receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV on days
      1 and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease
      progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on
      day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of
      disease progression or unacceptable toxicity.

      GROUP II (PET/CT-2 POSITIVE): Patients receive doxorubicin IV, vinblastine IV, dacarbazine,
      IV and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28
      days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
      Patients that are PET/CT negative receive nivolumab IV over 60 minutes on day 1. Treatment
      with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression
      or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 6 months for 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Group I Arm A (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 up to 3 cycles in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
  • Nivolumab
Group I Arm B (ABVD, nivolumab)ExperimentalPatients receive doxorubicin IV, bleomycin IV, vinblastine IV, dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
  • Bleomycin
  • Dacarbazine
  • Doxorubicin
  • Nivolumab
  • Vinblastine
Group II (AVD, brentuximab vedotin, nivolumab)ExperimentalPatients receive doxorubicin IV, vinblastine IV, dacarbazine, IV and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients that are PET/CT negative receive nivolumab IV over 60 minutes on day 1. Treatment with nivolumab repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
  • Brentuximab Vedotin
  • Dacarbazine
  • Doxorubicin
  • Nivolumab
  • Vinblastine

Eligibility Criteria

        Inclusion Criteria:

          -  Documented informed consent of the participant and/or legally authorized
             representative.

               -  Assent, when appropriate, will be obtained per institutional guidelines.

          -  Eastern Cooperative Oncology Group (ECOG) =< 2.

          -  Histologically confirmed diagnosis of classical Hodgkin lymphoma (cHL) by current
             World Health Organization classification (nodular sclerosis, mixed cellularity,
             lymphocyte rich, lymphocyte depleted, or classical Hodgkin lymphoma, NOS [not
             otherwise specified]) at local enrolling center. Nodular lymphocyte-predominant
             Hodgkin lymphoma is excluded

          -  Stage IA, IB, IIA, or IIB cHL by Cotswold modified Ann Arbor staging done prior to any
             treatment with ABVD.

          -  Must have prior to standard of care ABVD treatment at least one lesion that is > 1.5
             cm in the longest diameter on cross‐sectional imaging and measureable in two
             perpendicular dimensions on CT and fludeoxyglucose (FDG) avid by PET.

        Exclusion Criteria:

          -  Patients must be naive in terms of any prior therapy for Hodgkin lymphoma (including
             immunotherapy, chemotherapy or radiation therapy) with the exception that they may
             have received up to 2 cycles of ABVD as standard of care therapy prior to enrollment,
             as long as they can start protocol therapy (therapy administered in Arms A, B1/B2, or
             C) within timelines specified by the trial.

          -  Peripheral sensory neuropathy > grade 1 or any peripheral motor neuropathy.

          -  History of another primary malignancy that has not been in remission for at least 3
             years. (The following are exempt from the 3‐year limit: nonmelanoma skin cancer, fully
             excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and
             cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on
             Papanicolau [PAP] smear)

          -  Known cerebral/meningeal disease.

          -  History of progressive multifocal leukoencephalopathy (PML).

          -  Known history of pancreatitis.

          -  Documented history of a cerebral vascular event (stroke or transient ischemic attack),
             unstable angina, myocardial infarction, or cardiac symptoms consistent with New York
             Heart Association class III‐IV within 6 months prior to enrollment

          -  Uncontrolled cardiac disease including ventricular dysfunction, left ventricular
             ejection fraction < 45%, coronary artery disease, or arrhythmias.

          -  Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient
             contained in the drug formulation of brentuximab vedotin, nivolumab, or any component
             of ABVD.

          -  Known active infection with hepatitis B or hepatitis C. Patients who are hepatitis B
             carriers can enroll if have a negative hepatitis B polymerase chain reaction (PCR) DNA
             test and are on hepatitis B suppressive medication management with entecavir or
             lamivudine. Patients with past active hepatitis C virus (HCV) infection are eligible
             if they are PCR negative after curative therapy. Testing to be done only in patients
             suspected of having infections or exposures.

          -  Known active infection with human immunodeficiency virus (HIV). Patients who are HIV
             positive can enroll if CD4 count is > 200/uL and have an undetectable or
             unquantifiable HIV viral load within 28 days of enrollment, have concurrent management
             with infectious disease specialists, and are on stable combination antiretroviral
             therapy. Participants are required to be on antiretroviral regimens that are in
             accordance with the current International acquired immune deficiency syndrome (AIDS)
             Society guidelines concurrently with chemotherapy. The specific agents are at the
             discretion of the Investigator and the use of investigational agents currently
             available on an expanded access basis is allowed. Use of experimental antiretroviral
             agents or those containing zidovudine (including Combivir and Trizivir) or ritonavir
             (includes Norvir or Kaletra), Cobicistat, Didanosine (Videx or Videx EC), or similar
             potent CYP3 inhibitors are prohibited. In order to be eligible, participants taking
             zidovudine or ritonavir, Cobicistat, Didanosine, or other CYP3 inhibitors must change
             to a different regimen 7 days prior to therapy initiation. Changes to highly active
             antiretroviral therapy (HAART) therapy during the study may be made if medically
             necessary (toxicity, failure of regimen, etc.). Participants must be on HAART for at
             least 7 days prior to therapy. HIV testing to be done only in patients suspected of
             having infections or exposures

          -  Subjects with active interstitial pneumonitis.

          -  Subjects with active, known or suspected autoimmune disease. Subjects 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.

          -  Females only: pregnant or breastfeeding.

          -  Any other condition that would, in the investigator's judgment, contraindicate the
             patient's participation in the clinical study due to safety concerns with clinical
             study procedures.

          -  Prospective participants who, in the opinion of the investigator, may not be able to
             comply with all study procedures (including compliance issues related to
             feasibility/logistics).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:16 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:18-month Progression-free survival (PFS) for each arm of therapy
Time Frame:Up to 18 months
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.

Secondary Outcome Measures

Measure:Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
Time Frame:Up to 3 years
Safety Issue:
Description:Frequency tables will be used to summarize toxicity profile.
Measure:Scores from European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire C30, version 3 (EORTC-C30) for each arm of therapy
Time Frame:Up to 3 years
Safety Issue:
Description:All of the scales range in score from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning whereas a high score for a symptom scale or item represents a high level of symptomatology or problems.
Measure:Positron emission tomography/computed tomography‐2 negativity rate
Time Frame:After 2 courses of ABVD (each course is 28 days)
Safety Issue:
Description:
Measure:3-year PFS for each arm of treatment
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.
Measure:Overall survival for each arm of treatment
Time Frame:Up to 3 years
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:City of Hope Medical Center

Last Updated

November 22, 2019