Clinical Trials /

Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

NCT03646123

Description:

This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This study will have two parts. The drugs used in Part A are a targeted anticancer drug (brentuximab vedotin) and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs are referred to as "A+AVD." Participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment (12 doses). Part A will look at whether the drug combination reduces the number of patients who experience the side effect of febrile neutropenia. Febrile neutropenia is a very low white blood cell count and a fever, which can be life threatening. Part B will use brentuximab vedotin, plus nivolumab, doxorubicin, and dacarbazine. These four drugs are called "AN+AD." Participants will be given these drugs for up to 12 doses (up to 6 months). This part of the trial will look at whether this combination of drugs is safe and effective for treatment of cHL.

Related Conditions:
  • Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
  • Official Title: Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects

Clinical Trial IDs

  • ORG STUDY ID: SGN35-027
  • NCT ID: NCT03646123

Conditions

  • Hodgkin Lymphoma

Interventions

DrugSynonymsArms
brentuximab vedotinAdcetris, SGN-35A+AVD
doxorubicinA+AVD
vinblastineA+AVD
dacarbazineA+AVD
G-CSFfilgrastim, pegfilgrastimA+AVD
nivolumabOpdivoAN+AD

Purpose

This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This study will have two parts. The drugs used in Part A are a targeted anticancer drug (brentuximab vedotin) and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs are referred to as "A+AVD." Participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment (12 doses). Part A will look at whether the drug combination reduces the number of patients who experience the side effect of febrile neutropenia. Febrile neutropenia is a very low white blood cell count and a fever, which can be life threatening. Part B will use brentuximab vedotin, plus nivolumab, doxorubicin, and dacarbazine. These four drugs are called "AN+AD." Participants will be given these drugs for up to 12 doses (up to 6 months). This part of the trial will look at whether this combination of drugs is safe and effective for treatment of cHL.

Detailed Description

      Part A of this study will evaluate the impact of granulocyte colony stimulating factor
      primary prophylaxis (G-PP) administration during treatment with A+AVD on the incidence of
      febrile neutropenia, efficacy, and dose intensity in patients with advanced stage classical
      Hodgkin lymphoma (cHL). Participants will be treated using institutional standard of care
      practices for the majority of treatment decisions. A+AVD will be administered on days 1 and
      15 of a 28-day cycle, with the addition of G-PP 24-36 hours postdose. Participants will
      receive up to 6 cycles of treatment.

      Part B will evaluate the safety and tolerability of AN+AD. All drugs will be administered
      separately by IV infusion on Days 1 and 15 of each 28-day cycle for up to 6 cycles.
    

Trial Arms

NameTypeDescriptionInterventions
A+AVDExperimentalArm Description: Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle
  • brentuximab vedotin
  • doxorubicin
  • vinblastine
  • dacarbazine
  • G-CSF
AN+ADExperimentalBrentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion on Days 1 and 15 of each 28-day cycle
  • brentuximab vedotin
  • doxorubicin
  • dacarbazine
  • nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Treatment-naïve, Hodgkin lymphoma (HL) patients with Ann Arbor Stage 3 or 4 disease

          -  Histologically confirmed classical HL according to the current World Health
             Organization (WHO) Classification

          -  Bidimensional measureable disease as documented by PET/CT or CT imaging

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

        Exclusion Criteria:

          -  Nodular lymphocyte predominant HL

          -  History of another malignancy within 3 years of the first dose of study drug or any
             evidence of residual disease from a previously diagnosed malignancy. Exceptions are
             malignancies with a negligible risk of metastasis or death. Patients with nonmelanoma
             skin cancer, localized prostate cancer, or carcinoma in situ of any type are not
             excluded if they have undergone complete resection.

          -  Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy
             within 12 weeks of the first study drug dose, unless underlying disease has progressed
             on treatment

          -  Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or
             any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint
             pathways

          -  Active cerebral/meningeal disease related to the underlying malignancy

          -  Any active Grade 3 or higher viral, bacterial, or fungal infection within two weeks of
             the first dose of study drug (Grade 3 defined by the National Cancer Institute's
             Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03)

          -  Current therapy with other systemic anti-neoplastic or investigational agents

          -  Planned consolidative radiotherapy (Part B)

          -  Active interstitial lung disease that is symptomatic or may interfere with the
             detection or management of suspected drug-related pulmonary toxicity (Part B only)

          -  Grade 3 or higher pulmonary disease unrelated to underlying malignancy

          -  Idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon
             monoxide <50% predicted

          -  History of a cerebral vascular event within 6 months of first dose of study drug

          -  Child-Pugh B or C hepatic impairment

          -  Grade 2 or higher peripheral sensory or motor neuropathy

          -  Subjects with acute or chronic graft-versus-host-disease (GvHD) or receiving
             immunosuppressive therapy as treatment or as prophylaxis against GvHD

          -  Previous treatment with brentuximab vedotin

          -  Patients who are pregnant or breastfeeding

          -  Other serious condition that would impair the patient's ability to receive or tolerate
             the planned treatment and follow-up
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Febrile Neutropenia (FN) Rate (Part A)
Time Frame:Up to 6 months
Safety Issue:
Description:Proportion of patients with treatment-emergent incidence of FN

Secondary Outcome Measures

Measure:Primary Refractory Disease Rate (Part A)
Time Frame:Up to 9 months
Safety Issue:
Description:Proportion of patients with less than complete response (CR) or relapse within 3 months of end of treatment (EOT)
Measure:CR Rate (Part A)
Time Frame:Up to 6 months
Safety Issue:
Description:Proportion of patients with CR at EOT
Measure:Physician-reported Progression Free Survival (PFS) (Part A)
Time Frame:Up to 2 years
Safety Issue:
Description:The physician-reporting PFS is defined as the time from start of study treatment to first documentation of progression per investigator or to death due to any cause, whichever comes first.
Measure:Subsequent Anticancer Therapy Utilization Rate (Part A)
Time Frame:Up to 2.5 years
Safety Issue:
Description:Proportion of patients with subsequent anticancer therapies
Measure:Mean Dose Intensity (Part A)
Time Frame:Up to 6 months
Safety Issue:
Description:
Measure:Rate of Dose Reduction and Delays (Part A)
Time Frame:Up to 6 months
Safety Issue:
Description:Proportion of patients with dose reductions or delays related to any component of A+AVD
Measure:Incidence of adverse events (Part B)
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:Incidence of laboratory abnormalities (Part B)
Time Frame:Up to 2.5 years
Safety Issue:
Description:
Measure:Overall response rate (ORR) at EOT (Part B)
Time Frame:Up to 6 months
Safety Issue:
Description:ORR is defined as the proportion of participants with CR or partial response (PR) at EOT
Measure:Duration of response (DOR) (Part B)
Time Frame:Up to 2.5 years
Safety Issue:
Description:DOR is defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression per LYRIC or death, whichever comes first
Measure:Duration of complete response (DOCR) (Part B)
Time Frame:Up to 2.5 years
Safety Issue:
Description:DOCR is defined as the time from the first documentation of complete tumor response (CR) to the first documentation of tumor progression per LYRIC or death, whichever comes first. DOCR will only be calculated for the subgroup of subjects achieving CR.
Measure:Event-free survival (EFS) (Part B)
Time Frame:Up to 2.5 years
Safety Issue:
Description:EFS is defined as the time from start of study treatment to the first documentation of objective tumor progression, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or progressive disease, whichever comes first.
Measure:PFS (Part B)
Time Frame:Up to 2.5 years
Safety Issue:
Description:PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or death
Measure:Overall survival (OS) (Part B)
Time Frame:Up to 2.5 years
Safety Issue:
Description:Overall survival is defined as the time from start of study treatment to the date of death due to any cause

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Genetics, Inc.

Trial Keywords

  • Brentuximab vedotin
  • Doxorubicin
  • Vinblastine
  • Dacarbazine
  • Nivolumab

Last Updated

January 14, 2020