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Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

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ClinicalTrials.gov Identifier: NCT03646123
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : June 1, 2021
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Seagen Inc.

Tracking Information
First Submitted Date  ICMJE August 22, 2018
First Posted Date  ICMJE August 24, 2018
Last Update Posted Date June 1, 2021
Actual Study Start Date  ICMJE January 28, 2019
Estimated Primary Completion Date July 7, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 26, 2020)
  • Febrile Neutropenia (FN) Rate (Part A) [ Time Frame: Up to 6 months ]
    Proportion of patients with treatment-emergent incidence of FN.
  • Complete response (CR) rate (Parts B and C) [ Time Frame: Up to 6 months ]
    Proportion of participants with CR at end of treatment (EOT), according to the Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC).
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
Febrile Neutropenia (FN) Rate [ Time Frame: Up to 6 months ]
Proportion of patients with treatment-emergent incidence of FN
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 26, 2020)
  • Primary Refractory Disease Rate (Part A) [ Time Frame: Up to 9 months ]
    Proportion of participants with less than CR or relapse within 3 months of EOT.
  • CR Rate (Part A) [ Time Frame: Up to 6 months ]
    Proportion of patients with CR at EOT.
  • Physician-reported Progression Free Survival (PFS) (Part A) [ Time Frame: 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.
  • Subsequent Anticancer Therapy Utilization Rate (Part A) [ Time Frame: Up to 2.5 years ]
    Proportion of patients with subsequent anticancer therapies.
  • Mean Dose Intensity (Part A) [ Time Frame: Up to 6 months ]
  • Rate of Dose Reduction and Delays (Part A) [ Time Frame: Up to 6 months ]
    Proportion of patients with dose reductions or delays related to any component of A+AVD.
  • Incidence of adverse events (Parts B and C) [ Time Frame: Up to 7 months ]
  • Incidence of laboratory abnormalities (Parts B and C) [ Time Frame: Up to 7 months ]
  • Overall response rate (ORR) at EOT (Parts B and C) [ Time Frame: Up to 6 months ]
    ORR is defined as the proportion of participants with CR or partial response (PR) at EOT.
  • Duration of response (DOR) (Parts B and C) [ Time Frame: 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.
  • Duration of complete response (DOCR) (Parts B and C) [ Time Frame: 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.
  • Event-free survival (EFS) (Parts B and C) [ Time Frame: 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.
  • PFS (Parts B and C) [ Time Frame: Up to 5 years ]
    PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or death.
  • Overall survival (OS) (Parts B and C) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2018)
  • Primary Refractory Disease Rate [ Time Frame: Up to 9 months ]
    Proportion of patients with less than complete response (CR) or relapse within 3 months of end of treatment (EOT)
  • CR Rate [ Time Frame: Up to 6 months ]
    Proportion of patients with CR at EOT
  • Physician-reported Progression Free Survival (PFS) [ Time Frame: Up to 2.5 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.
  • Subsequent Anticancer Therapy Utilization Rate [ Time Frame: Up to 2.5 years ]
    Proportion of patients with subsequent anticancer therapies
  • Mean Dose Intensity [ Time Frame: Up to 6 months ]
  • Rate of Dose Reduction and Delays [ Time Frame: Up to 6 months ]
    Proportion of patients with dose reductions or delays related to any component of A+AVD
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
Official Title  ICMJE Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects
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.

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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hodgkin Lymphoma
Intervention  ICMJE
  • 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
  • Drug: nivolumab
    240 mg by IV infusion
    Other Name: Opdivo
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: brentuximab vedotin
    • Drug: doxorubicin
    • Drug: vinblastine
    • Drug: dacarbazine
    • Drug: G-CSF
  • 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.
    Interventions:
    • Drug: brentuximab vedotin
    • Drug: doxorubicin
    • Drug: dacarbazine
    • Drug: nivolumab
  • 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.
    Interventions:
    • Drug: brentuximab vedotin
    • Drug: doxorubicin
    • Drug: dacarbazine
    • Drug: nivolumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 26, 2020)
240
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2018)
180
Estimated Study Completion Date  ICMJE June 7, 2026
Estimated Primary Completion Date July 7, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Seagen Trial Information Support 866-333-7436 clinicaltrials@seagen.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03646123
Other Study ID Numbers  ICMJE SGN35-027
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Seagen Inc.
Study Sponsor  ICMJE Seagen Inc.
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Study Director: Linda Ho, MD Seagen Inc.
PRS Account Seagen Inc.
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP