Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies

Study Overview
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Brief Summary
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This is an open-label, multicenter, phase 2 clinical trial to evaluate the antitumor activity of brentuximab vedotin as a single agent in patients with CD30-positive nonlymphomatous malignancies.

Official Title
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A Phase 2, Open-label Study of Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies

Conditions
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Acute Lymphoid Leukemia, Acute Myeloid Leukemia, Anemia, Refractory, With Excess of Blasts, Solid Tumors

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: brentuximab vedotin
* Drug: brentuximab vedotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-confirmed by central review CD30-positive nonlymphomatous malignancy Have failed, refused, or have been deemed ineligible for standard therapy Measurable disease Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 or a Karnofsky or Lansky Performance Status score greater than or equal to 70 Exclusion Criteria: Primary diagnosis of lymphoma or central nervous system (CNS) malignancy History of another primary invasive malignancy that has not been definitively treated or in remission for at least 3 years Evidence of active cerebral/meningeal disease

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab vedotin 1.8 mg/kg<br>Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by intravenous (IV) infusion<br>* Other names: Adcetris; SGN-35;|
| Experimental: Brentuximab vedotin 2.4 mg/kg<br>Brentuximab vedotin 2.4 mg/kg every 3 weeks by IV infusion | Drug: brentuximab vedotin<br>* 2.4 mg/kg every 3 weeks by intravenous (IV) infusion<br>* Other names: Adcetris; SGN-35;|
| Experimental: Brentuximab vedotin 1.2 mg/kg<br>Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by IV infusion | Drug: brentuximab vedotin<br>* 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion<br>* Other names: Adcetris; SGN-35;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Investigator | Percentage of participants who achieved a best response of complete response/remission (CR), CR without hematologic recovery (CRi; leukemia only), or partial remission (PR) per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003). | Up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Remission (CR) Rate by Investigator | Percentage of participants who achieved a best response of CR per the applicable response criteria. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003). | Up to approximately 3 years | 
| Duration of Objective Response by Kaplan-Meier Analysis | Duration of objective response (CR [+CRi; leukemia] + PR), defined as time of initial response until disease progression or death. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003). | Up to approximately 2 years | 
| Duration of Complete Response by Kaplan-Meier Analysis | Duration of CR, defined as time of initial response until disease progression or death. Response criteria for solid tumors (by radiographic tumor imaging) per Response Evaluation Criteria for Solid Tumors (RECIST) 1.1 (Eisenhauer 2009); response criteria for leukemia (by peripheral blood and bone marrow aspirate or biopsy) per International Working Group (Cheson 2003). | Up to approximately 2 years | 
| Progression-Free Survival by Kaplan-Meier Analysis | Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause | Up to approximately 2 years | 
| Adverse Events by Severity, Seriousness, and Relationship to Treatment | Counts of participants who had treatment-emergent adverse events (TEAE, defined as newly occurring or worsening after first dose on Study SGN35-013). Serious adverse events are reported from the time of informed consent. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.03) were used to assess severity (1=mild, 2=moderate, 3=severe, 4=life-threatening/disabling, 5=fatal). Relatedness to study drug was assessed by the investigator (Yes/No). Participants with multiple occurrences of an adverse event within a category are counted once within the category. | Up to approximately 3 years | 
| Laboratory Abnormalities >/= Grade 3 | Counts of study participants with post-baseline laboratory abnormalities of Grade 3 or greater per NCI CTCAE version 4.03. Participants with multiple occurrences of a laboratory abnormality within a category are counted once in that category | Up to approximately 3 years | 
| Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) |  | Up to approximately 3 years | 
| Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) |  | Up to approximately 3 years | 
| Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) |  | Up to approximately 3 years | 
| Brentuximab Vedotin Monomethyl Auristatin E (MMAE) Trough Concentration (Ctrough) |  | Up to approximately 3 years | 
| Incidence of Anti-therapeutic Antibodies (ATA) | Counts of participants with post-baseline anti-brentuximab vedotin antibodies. Persistently positive is defined as confirmed ATA in more than 2 post-baseline samples and transiently positive is defined as confirmed ATA in 1 or 2 post-baseline samples. | Up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Lymphoid Leukemia, Myelodysplastic Syndrome, Acute Myeloid Leukemia, Solid Tumors, Anemia, Refractory, with Excess of Blasts, Antibodies, Monoclonal, Antibody-Drug Conjugate, Antigens, CD30, Drug Therapy, Hematologic Diseases, Immunotherapy, Monomethyl Auristatin E