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Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03646123
Recruitment Status : Recruiting
First Posted : August 24, 2018
Last Update Posted : May 28, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Seattle Genetics, Inc.

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 disease Intervention/treatment Phase
Hodgkin Lymphoma Drug: brentuximab vedotin Drug: doxorubicin Drug: vinblastine Drug: dacarbazine Drug: G-CSF Drug: nivolumab 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : January 28, 2019
Estimated Primary Completion Date : July 7, 2022
Estimated Study Completion Date : June 7, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/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 Name: 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 Name: Opdivo




Primary Outcome Measures :
  1. Febrile Neutropenia (FN) Rate (Part A) [ Time Frame: Up to 6 months ]
    Proportion of patients with treatment-emergent incidence of FN.

  2. 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).


Secondary Outcome Measures :
  1. 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.

  2. CR Rate (Part A) [ Time Frame: Up to 6 months ]
    Proportion of patients with CR at EOT.

  3. 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.

  4. Subsequent Anticancer Therapy Utilization Rate (Part A) [ Time Frame: Up to 2.5 years ]
    Proportion of patients with subsequent anticancer therapies.

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

  7. Incidence of adverse events (Parts B and C) [ Time Frame: Up to 7 months ]
  8. Incidence of laboratory abnormalities (Parts B and C) [ Time Frame: Up to 7 months ]
  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 II 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 with non-bulky mediastinal disease
  • Histologically confirmed cHL according to the current World Health Organization (WHO) Classification
  • Bidimensional measurable 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 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 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 (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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03646123


Contacts
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Contact: Seattle Genetics Trial Information Support 866-333-7436 clinicaltrials@seagen.com

Locations
Show Show 22 study locations
Sponsors and Collaborators
Seattle Genetics, Inc.
Bristol-Myers Squibb
Investigators
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Study Director: Linda Ho, MD Seattle Genetics, Inc.
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Responsible Party: Seattle Genetics, Inc.
ClinicalTrials.gov Identifier: NCT03646123    
Other Study ID Numbers: SGN35-027
First Posted: August 24, 2018    Key Record Dates
Last Update Posted: May 28, 2020
Last Verified: May 26, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seattle Genetics, Inc.:
Brentuximab vedotin
Doxorubicin
Vinblastine
Dacarbazine
Nivolumab
Additional relevant MeSH terms:
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Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Doxorubicin
Nivolumab
Dacarbazine
Vinblastine
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antineoplastic Agents, Alkylating
Alkylating Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators