Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

Sponsor
Seagen Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03646123
Collaborator
Bristol-Myers Squibb (Industry)
240
Enrollment
66
Locations
3
Arms
88.3
Anticipated Duration (Months)
3.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This trial will find out if these two treatment combinations work to treat cHL. It will also find out what side effects occur. A side effect is anything the drug does besides treating cancer. This study will have three parts (Parts A, B, and C).

The drugs used in Part A are a combination of targeted anticancer drug (brentuximab vedotin) and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs are called "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 A+AVD drug combination reduces the number of participants 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.

Parts B and C will use drug combination of brentuximab vedotin, plus nivolumab, doxorubicin, and dacarbazine. These four drugs are called "AN+AD." Parts B and C will study how well the drugs work to treat cHL and what side effects they cause.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

This study will have three parts.

Part A of the study is designed to evaluate the incidence of febrile neutropenia, efficacy, and dose intensity in participants with advanced stage classical Hodgkin lymphoma (cHL) receiving granulocyte colony stimulating factor primary prophylaxis (G-PP) administration during treatment with frontline A+AVD. In Part A, participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment. Participants will be treated using institutional standard of care practices for the majority of treatment decisions.

Part B is designed to evaluate the combination of brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) as frontline treatment in participants with advanced cHL. In Part B, participants will be given AN+AD combination for 6 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage II with bulky mediastinal disease and Stage III or IV cHL.

Part C is designed to evaluate AN+AD as frontline treatment in participants with early stage cHL. In Part C, participants will be given AN+AD combination for 4 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage I or II cHL with non-bulky mediastinal disease.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
240 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects
Actual Study Start Date :
Jan 28, 2019
Anticipated Primary Completion Date :
Jul 7, 2022
Anticipated Study Completion Date :
Jun 7, 2026

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part A: A+AVD

Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle.

Drug: brentuximab vedotin
1.2 mg/kg by IV infusion
Other Names:
  • Adcetris
  • SGN-35
  • Drug: doxorubicin
    25 mg/m^2 by IV infusion

    Drug: vinblastine
    6 mg/m^2 by IV infusion

    Drug: dacarbazine
    375 mg/m^2 by IV infusion

    Drug: G-CSF
    Granulocyte colony stimulating factor (G-CSF) primary prophylaxis administered 24-36 hours after each dose of A+AVD
    Other Names:
  • filgrastim
  • pegfilgrastim
  • Experimental: Part B: AN+AD

    Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage II bulky mediastinal disease and Stage III or IV cHL during each treatment cycle.

    Drug: brentuximab vedotin
    1.2 mg/kg by IV infusion
    Other Names:
  • Adcetris
  • SGN-35
  • Drug: doxorubicin
    25 mg/m^2 by IV infusion

    Drug: dacarbazine
    375 mg/m^2 by IV infusion

    Drug: nivolumab
    240 mg by IV infusion
    Other Names:
  • Opdivo
  • Experimental: Part C: AN+AD

    Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage I or II cHL with non-bulky mediastinal disease during each treatment cycle.

    Drug: brentuximab vedotin
    1.2 mg/kg by IV infusion
    Other Names:
  • Adcetris
  • SGN-35
  • Drug: doxorubicin
    25 mg/m^2 by IV infusion

    Drug: dacarbazine
    375 mg/m^2 by IV infusion

    Drug: nivolumab
    240 mg by IV infusion
    Other Names:
  • Opdivo
  • Outcome Measures

    Primary Outcome Measures

    1. Febrile Neutropenia (FN) Rate (Part A) [Up to 6 months]

      Proportion of patients with treatment-emergent incidence of FN.

    2. Complete response (CR) rate (Parts B and C) [Up to 6 months]

      Proportion of participants with CR at end of treatment (EOT), according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).

    Secondary Outcome Measures

    1. Primary Refractory Disease Rate (Part A) [Up to 9 months]

      Proportion of participants with less than CR or relapse within 3 months of EOT.

    2. CR Rate (Part A) [Up to 6 months]

      Proportion of patients with CR at EOT.

    3. Physician-reported Progression Free Survival (PFS) (Part A) [Up to 2 years]

      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.

    4. Subsequent Anticancer Therapy Utilization Rate (Part A) [Up to 2.5 years]

      Proportion of patients with subsequent anticancer therapies.

    5. Mean Dose Intensity (Part A) [Up to 6 months]

    6. Rate of Dose Reduction and Delays (Part A) [Up to 6 months]

      Proportion of patients with dose reductions or delays related to any component of A+AVD.

    7. Incidence of adverse events (Parts B and C) [Up to 7 months]

    8. Incidence of laboratory abnormalities (Parts B and C) [Up to 7 months]

    9. Overall response rate (ORR) at EOT (Parts B and C) [Up to 6 months]

      ORR is defined as the proportion of participants with CR or partial response (PR) at EOT.

    10. Duration of response (DOR) (Parts B and C) [Up to 5 years]

      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.

    11. Duration of complete response (DOCR) (Parts B and C) [Up to 5 years]

      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.

    12. Event-free survival (EFS) (Parts B and C) [Up to 5 years]

      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.

    13. PFS (Parts B and C) [Up to 5 years]

      PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or death.

    14. Overall survival (OS) (Parts B and C) [Up to 5 years]

      Overall survival is defined as the time from start of study treatment to the date of death due to any cause.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Inclusion Criteria

    • Treatment-naïve, classic Hodgkin lymphoma (cHL) participants

    • Participants enrolling in Part A of the study must have Ann Arbor Stage III or IV disease

    • Participants enrolling in Part B of the study must have Ann Arbor Stage I or II cH: with bulky mediastinal disease, or Stage III or IV

    • Participants enrolling in Part C of the study must have Ann Arbor Stage I or II cHL without bulky disease

    • Histologically confirmed cHL according to the current World Health Organization (WHO) Classification

    • Bidimensional measurable disease as documented by PET/CT or CT imaging

    • Age 12 years or older in the United States. For regions outside of the US, participants must 18 years or older.

    • 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 or metastasis or death. Participants 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 4 weeks of the first study drug dose

    • 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 (Parts B and C only)

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

    • Grade 3 or higher pulmonary disease unrelated to underlying malignancy

    • Documented history of 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

    • Participants 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

    • Participants who are pregnant or breastfeeding

    • Other serious condition that would impair the participant's ability to receive or tolerate the planned treatment and follow-up

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Compassionate Care Research GroupFountain ValleyCaliforniaUnited States92708
    2Rocky Mountain Cancer Centers - AuroraAuroraColoradoUnited States80012
    3University of Colorado Health Memorial HospitalColorado SpringsColoradoUnited States80909
    4Cancer Centers of Colorado - DenverDenverColoradoUnited States80218
    5Poudre Valley Health System (PVHS)Fort CollinsColoradoUnited States80528
    6SCL Health - St. Mary's Hospital & Medical CenterGrand JunctionColoradoUnited States81501
    7Miami Cancer Institute at Baptist Health, Inc.MiamiFloridaUnited States33176
    8Florida Cancer Specialists - North RegionSaint PetersburgFloridaUnited States33705
    9Illinois Cancer CarePeoriaIllinoisUnited States61615
    10Massachusetts General HospitalBostonMassachusettsUnited States02114
    11Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
    12Karmanos Cancer Institute / Wayne State UniversityDetroitMichiganUnited States48201
    13Henry Ford Health SystemDetroitMichiganUnited States48202
    14Minnesota Oncology Hematology P.A.EdinaMinnesotaUnited States55435
    15Washington University in St LouisSaint LouisMissouriUnited States63110
    16New Jersey Hematology Oncology Associates, LLCBrickNew JerseyUnited States08724
    17Regional Cancer Care Associates - FreeholdFreeholdNew JerseyUnited States07728
    18Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    19Regional Cancer Care Associates - HowellHowellNew JerseyUnited States07731
    20Morristown Medical Center/ Carol G. Simon Cancer CenterMorristownNew JerseyUnited States07960
    21Regional Cancer Care Associates - Mount HollyMount HollyNew JerseyUnited States08060
    22Regional Cancer Care Associates - Central JerseySomervilleNew JerseyUnited States08876
    23Regional Cancer Care Associates - SpartaSpartaNew JerseyUnited States07871
    24New York Oncology Hematology, P.C.AlbanyNew YorkUnited States12208
    25CareMount Medical GroupMount KiscoNew YorkUnited States10549-3412
    26Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10065
    27Clinical Research Alliance - Abraham Mittelman, MD, LLCPurchaseNew YorkUnited States10577
    28Clinical Research Alliance - Morton Coleman, MDWestburyNew YorkUnited States11590
    29Wake Forest Baptist Medical Center / Wake Forest UniversityWinston-SalemNorth CarolinaUnited States27157
    30Oncology Hematology CareCincinnatiOhioUnited States45242
    31Case Western Reserve University / University Hospitals Cleveland Medical CenterClevelandOhioUnited States44106
    32Cleveland Clinic, TheClevelandOhioUnited States44195
    33Toledo Clinic Cancer CenterToledoOhioUnited States43623
    34Willamette Valley Cancer Institute/Oncology Assc of OregonEugeneOregonUnited States97401
    35Providence Portland Medical CenterPortlandOregonUnited States97213
    36Medical University of South Carolina/Hollings Cancer CenterCharlestonSouth CarolinaUnited States29425
    37University of TennesseeKnoxvilleTennesseeUnited States37920
    38Tennessee Oncology - NashvilleNashvilleTennesseeUnited States37203
    39Texas Oncology - Austin MidtownAustinTexasUnited States78705
    40Texas Oncology - Medical City DallasDallasTexasUnited States75230
    41Texas Oncology - Flower MoundFlower MoundTexasUnited States75028
    42Brooke Army Medical CenterFort Sam HoustonTexasUnited States78234
    43Texas Oncology - Fort Worth 12th AvenueFort WorthTexasUnited States76104
    44MD Anderson Cancer Center / University of TexasHoustonTexasUnited States77030-4095
    45Texas Oncology - San Antonio Medical CenterSan AntonioTexasUnited States78240
    46Texas Oncology - TylerTylerTexasUnited States75702
    47Huntsman Cancer Institute/University of UtahSalt Lake CityUtahUnited States84112
    48Virginia Cancer Specialists, PCFairfaxVirginiaUnited States22031
    49Oncology and Hematology Assoc of SW VA DBA Blue Ridge Cancer CareSalemVirginiaUnited States24153
    50Kadlec Clinic Hematology and OncologyKennewickWashingtonUnited States99336
    51Vista Oncology Inc PSOlympiaWashingtonUnited States98506
    52Seattle Cancer Care Alliance / University of WashingtonSeattleWashingtonUnited States98109-1023
    53Royal Adelaide HospitalAdelaideOtherAustralia5000
    54Ballarat Regional Integrated Cancer CareBallaratOtherAustralia3350
    55Monash Medical CentreClaytonOtherAustralia3168
    56Epworth HealthcareVictoriaOtherAustralia3002
    57Azienda Ospedaliera Spedali Civili di BresciaBresciaOtherItaly25123
    58Hospital del MarBarcelonaOtherSpain08003
    59Hospital Duran i Reynals - Institut Catala d'OncologiaBarcelonaOtherSpain08908
    60Hospital Universitario de Girona Doctor Josep TruetaGironaOtherSpain17007
    61Hospital Universitario Fundacion Jimenez DiazMadridOtherSpain28040
    62Hospital Universitario 12 de OctubreMadridOtherSpain28041
    63Hospital Puerta de Hierro MajadahondaMajadahondaOtherSpain28222
    64Hospital Universitario Central de AsturiasOviedoOtherSpain33011
    65Hospital Universitario de SalamancaSalamancaOtherSpain37007
    66Hospital Universitari i Politecnic La Fe de ValenciaValenciaOtherSpain46026

    Sponsors and Collaborators

    • Seagen Inc.
    • Bristol-Myers Squibb

    Investigators

    • Study Director: Linda Ho, MD, Seagen Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Seagen Inc.
    ClinicalTrials.gov Identifier:
    NCT03646123
    Other Study ID Numbers:
    • SGN35-027
    First Posted:
    Aug 24, 2018
    Last Update Posted:
    Nov 23, 2021
    Last Verified:
    Nov 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Seagen Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Nov 23, 2021