The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

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Hematological Malignancies

Brentuximab vedotin

Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects
Phase 2
NCT03646123

Active Not-enrolling

Globe
Locations

United States, Australia, Czechia, Italy, Poland, Spain

Study design

Participant Group/Arm

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.

Intervention/Treatment

DRUG: brentuximab vedotin

1.2 mg/kg by IV infusion

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

Participant Group/Arm

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.

Intervention/Treatment

DRUG: brentuximab vedotin

1.2 mg/kg by IV infusion

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

Participant Group/Arm

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.

Intervention/Treatment

DRUG: brentuximab vedotin

1.2 mg/kg by IV infusion

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

Key eligibility criteria

Inclusion 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 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 disea
  • 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
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

Key dates

Study start date
  • January 2019
Estimated primary completion date
  • June 2026

Key endpoints

Primary Outcome Measures
Outcome Measure

Febrile Neutropenia (FN) Rate (Part A)

Measure Description

The FN rate is defined as the number of participants who experience treatment-emergent FN.

Time Frame

7.5 months

Outcome Measure

Complete Response (CR) Rate (Parts B and C)

Measure Description

CR rate at EOT is defined as the percentage of subjects with CR at EOT, according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016), in subjects with previously untreated cHL.

Time Frame

7.8 months

Secondary Outcome Measures:
Outcome Measure

Primary Refractory Disease Rate (Part A)

Measure Description

The primary refractory disease rate is defined as the percentage of participants with less than complete response or relapse within 3 months of EOT, according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas

Time Frame

10.2 months

Outcome Measure

Complete Response Rate (Part A)

Measure Description

The complete response rate is defined as the percentage of participants with CR at EOT according to the Lugano Classification Revised Staging System for nodal non-Hodgkin and Hodgkin lymphomas (Cheson 2014).

Time Frame

7.2 months

Outcome Measure

Physician-reported Progression Free Survival (PFS) (Part A)

Measure Description

The physician-reported PFS rate at 2 years is estimated based on Kaplan-Meier methodology.

Time Frame

24 months

Outcome Measure

Subsequent Anticancer Therapy Utilization Rate (Part A)

Measure Description

Number of participants with subsequent anticancer therapy

Time Frame

33.8 months

Outcome Measure

Actual Dose Intensity: Brentuximab Vedotin (Part A)

Time Frame

6.5 months

Outcome Measure

Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A)

Time Frame

6.5 months

Outcome Measure

Relative Dose Intensity (Part A)

Time Frame

6.5 months

Outcome Measure

Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A)

Time Frame

6.5 months

Outcome Measure

Rate of Dose Reduction and Delays: Doxorubicin (Part A)

Time Frame

6.5 months

Outcome Measure

Rate of Dose Reduction and Delays: Vinblastine (Part A)

Time Frame

6.5 months

Outcome Measure

Rate of Dose Reduction and Delays: Dacarbazine (Part A)

Time Frame

6.5 months

Outcome Measure

Incidence of Adverse Events (Parts B and C)

Time Frame

8.9 months

Outcome Measure

Incidence of Laboratory Abnormalities (Parts B and C)

Measure Description

Laboratory values were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE version 4.03).

Time Frame

8.9 months

Outcome Measure

Overall Response Rate (ORR) at EOT (Parts B and C)

Measure Description

ORR is defined as the proportion of participants with CR or partial response (PR) at EOT according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of LYRIC (Cheson 2016) in subjects with previously untreated cHL.

Time Frame

7.8 months

Number of participants

255

Collaborators and investigators

Sponsor: Seagen Inc.

Collaborator: Bristol-Myers Squibb

This information is current as of May 28th 2024.