Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Acute Lymphoid Leukemia; Acute Myeloid Leukemia; Anemia, Refractory, With Excess of Blasts; Solid Tumors	Drug: brentuximab vedotin	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	84 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2, Open-label Study of Brentuximab Vedotin in Patients With CD30-positive Nonlymphomatous Malignancies
Study Start Date :	October 2011
Actual Primary Completion Date :	December 2014
Actual Study Completion Date :	December 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Brentuximab vedotin 1.8 mg/kg; Brentuximab vedotin 1.8 mg/kg every 3 weeks by IV infusion	Drug: brentuximab vedotin; 1.8 mg/kg every 3 weeks by intravenous (IV) infusion; Other Name: Adcetris; SGN-35
Experimental: Brentuximab vedotin 2.4 mg/kg; Brentuximab vedotin 2.4 mg/kg every 3 weeks by IV infusion	Drug: brentuximab vedotin; 2.4 mg/kg every 3 weeks by intravenous (IV) infusion; Other Name: Adcetris; SGN-35
Experimental: Brentuximab vedotin 1.2 mg/kg; Brentuximab vedotin 1.2 mg/kg weekly, 3 out of 4 weeks, by IV infusion	Drug: brentuximab vedotin; 1.2 mg/kg weekly, 3 out of 4 weeks, by intravenous (IV) infusion; Other Name: Adcetris; SGN-35

Outcome Measures

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Primary Outcome Measures :

1. Objective Response Rate (ORR) by Investigator [ Time Frame: Up to approximately 3 years ]
   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).

Secondary Outcome Measures :

1. Complete Remission (CR) Rate by Investigator [ Time Frame: Up to approximately 3 years ]
   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).
2. Duration of Objective Response by Kaplan-Meier Analysis [ Time Frame: Up to approximately 2 years ]
   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).
3. Duration of Complete Response by Kaplan-Meier Analysis [ Time Frame: Up to approximately 2 years ]
   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).
4. Progression-Free Survival by Kaplan-Meier Analysis [ Time Frame: Up to approximately 2 years ]
   Progression-free survival, defined as time from start of study treatment to disease progression per investigator or death due to any cause
5. Adverse Events by Severity, Seriousness, and Relationship to Treatment [ Time Frame: Up to approximately 3 years ]
   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.
6. Laboratory Abnormalities >/= Grade 3 [ Time Frame: Up to approximately 3 years ]
   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
7. Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Concentration at End of Infusion (Ceoi) [ Time Frame: Up to approximately 3 years ]
8. Brentuximab Vedotin Antibody-Drug Conjugate (ADC) Trough Concentration (Ctrough) [ Time Frame: Up to approximately 3 years ]
9. Maximum Concentration (Cmax) of Brentuximab Vedotin Monomethyl Auristatin E (MMAE) [ Time Frame: Up to approximately 3 years ]
10. Brentuximab Vedotin Monomethyl Auristatin E (MMAE) Trough Concentration (Ctrough) [ Time Frame: Up to approximately 3 years ]
11. Incidence of Anti-therapeutic Antibodies (ATA) [ Time Frame: Up to approximately 3 years ]
    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.

Eligibility Criteria

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Ages Eligible for Study:	6 Years and older (Child, Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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  Show 29 Study Locations

Sponsors and Collaborators

Seattle Genetics, Inc.

Investigators

Study Director:	Neil Josephson, MD	Seattle Genetics, Inc.

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Borate U, Mehta A, Reddy V, Tsai M, Josephson N, Schnadig I. Treatment of CD30-positive systemic mastocytosis with brentuximab vedotin. Leuk Res. 2016 May;44:25-31. doi: 10.1016/j.leukres.2016.02.010. Epub 2016 Feb 27.

Giannatempo P, Paolini B, Miceli R, Raggi D, Nicolai N, Farè E, Catanzaro M, Biasoni D, Torelli T, Stagni S, Piva L, Mariani L, Salvioni R, Colecchia M, Gianni AM, Necchi A. Persistent CD30 expression by embryonal carcinoma in the treatment time course: prognostic significance of a worthwhile target for personalized treatment. J Urol. 2013 Nov;190(5):1919-24. doi: 10.1016/j.juro.2013.04.057. Epub 2013 Apr 25.

Responsible Party:	Seattle Genetics, Inc.
ClinicalTrials.gov Identifier:	NCT01461538 History of Changes
Other Study ID Numbers:	SGN35-013
First Posted:	October 28, 2011
Results First Posted:	March 4, 2016
Last Update Posted:	March 4, 2016
Last Verified:	February 2016

Keywords provided by Seattle Genetics, Inc.:

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

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Refractory, with Excess of Blasts; Anemia, Refractory; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases	Immunoproliferative Disorders; Immune System Diseases; Anemia; Hematologic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Antibodies; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs