A Phase 1 Study of Brentuximab Vedotin Given Sequentially and Combined With Multi-Agent Chemotherapy for CD30-Positive Mature T-Cell and NK-Cell Neoplasms

Sponsor

Seagen Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01309789

Collaborator

Millennium Pharmaceuticals, Inc. (Industry)

Enrollment

Locations

Arms

72.9

Duration (Months)

3.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety profile of brentuximab vedotin sequentially and in combination with multi-agent chemotherapy in front-line treatment for CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma. It is a phase 1, open-label, dose escalation study in three arms designed to define the MTD, PK, immunogenicity, and anti-tumor activity of brentuximab vedotin in sequence and in combination with multi-agent front-line chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Large-Cell, Anaplastic Lymphoma, NK-cell Lymphoma, T-cell	Drug: brentuximab vedotin Drug: cyclophosphamide Drug: brentuximab vedotin Drug: prednisone Drug: cyclophosphamide Drug: doxorubicin Drug: doxorubicin Drug: prednisone Drug: vincristine	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

39 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of Brentuximab Vedotin Administered Sequentially and Concurrently With Multi-Agent Chemotherapy as Front-Line Therapy in Patients With CD30-Positive Mature T-Cell and NK-Cell Neoplasms, Including Systemic Anaplastic Large Cell Lymphoma

Study Start Date :

Feb 1, 2011

Actual Primary Completion Date :

Apr 1, 2013

Actual Study Completion Date :

Feb 28, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Sequential	Drug: brentuximab vedotin 1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-2 and if response, Cycles 9-16) Other Names: SGN-35 Drug: cyclophosphamide 750 mg/m2 IV every 3 weeks (Cycles 3-8) Drug: prednisone 100 mg daily PO on Days 1-5 every 3 weeks (Cycles 3-8) Drug: doxorubicin 50 mg/m2 IV every 3 weeks (Cycles 3-8) Drug: vincristine 1.4 mg/m2 IV every 3 weeks (Cycles 3-8)
Experimental: 2 Combination	Drug: brentuximab vedotin 1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-6 and if response, Cycles 7-16) Other Names: SGN-35 Drug: cyclophosphamide 750 mg/m2 IV every 3 weeks (Cycles 1-6) Drug: doxorubicin 50 mg/m2 IV every 3 weeks (Cycles 1-6) Drug: prednisone 100 mg daily PO on Days 1-5 every 3 weeks (Cycles 1-6)
Experimental: 3 Brentuximab vedotin/CH-P Combination	Drug: brentuximab vedotin 1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-6 and if response, Cycles 7-16) Other Names: SGN-35 Drug: cyclophosphamide 750 mg/m2 IV every 3 weeks (Cycles 1-6) Drug: doxorubicin 50 mg/m2 IV every 3 weeks (Cycles 1-6) Drug: prednisone 100 mg daily PO on Days 1-5 every 3 weeks (Cycles 1-6)

Arm

Intervention/Treatment

Experimental: 1

Sequential

Drug: brentuximab vedotin

1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-2 and if response, Cycles 9-16)

Other Names:

SGN-35

Drug: cyclophosphamide

750 mg/m2 IV every 3 weeks (Cycles 3-8)

Drug: prednisone

100 mg daily PO on Days 1-5 every 3 weeks (Cycles 3-8)

Drug: doxorubicin

50 mg/m2 IV every 3 weeks (Cycles 3-8)

Drug: vincristine

1.4 mg/m2 IV every 3 weeks (Cycles 3-8)

Experimental: 2

Combination

Drug: brentuximab vedotin

1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-6 and if response, Cycles 7-16)

Other Names:

SGN-35

Drug: cyclophosphamide

750 mg/m2 IV every 3 weeks (Cycles 1-6)

Drug: doxorubicin

50 mg/m2 IV every 3 weeks (Cycles 1-6)

Drug: prednisone

100 mg daily PO on Days 1-5 every 3 weeks (Cycles 1-6)

Experimental: 3 Brentuximab vedotin/CH-P

Combination

Drug: brentuximab vedotin

1.2-1.8 mg/kg IV every 3 weeks (Cycles 1-6 and if response, Cycles 7-16)

Other Names:

SGN-35

Drug: cyclophosphamide

750 mg/m2 IV every 3 weeks (Cycles 1-6)

Drug: doxorubicin

50 mg/m2 IV every 3 weeks (Cycles 1-6)

Drug: prednisone

100 mg daily PO on Days 1-5 every 3 weeks (Cycles 1-6)

Outcome Measures

Primary Outcome Measures

Incidence of adverse events and laboratory abnormalities [Through 1 month after last dose]

Secondary Outcome Measures

Brentuximab vedotin concentration in blood [Through 1 month after last dose]
Antitherapeutic antibodies in blood [Through 1 month after last dose]
Best clinical response [Through 1 month after last dose]
Progression-free survival [Until disease progression or study closure]
Overall survival [Every 3 months until death or study closure]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Treatment-naive CD30-positive mature T-cell and NK-cell neoplasms, including systemic anaplastic large cell lymphoma
Measurable disease of at least 1.5 cm
ECOG performance status less than or equal to 2

Exclusion Criteria:

Known cerebral/meningeal disease, including history of progressive multifocal leukoencephalopathy
Current diagnosis of primary cutaneous anaplastic large cell lymphoma, mycosis fungoides, Sezary syndrome or other primary cutaneous lymphomas; extranodal NK/T-cell lymphoma, nasal type
History of another primary malignancy that has not been in remission for at least 3 years
Left ventricular ejection fraction <45% or symptomatic cardiac disease, or myocardial infarction within the past 12 months
Viral, bacterial, or fungal infection within two weeks prior to the first dose of brentuximab vedotin
Known human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus positive status

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35294-3300
2	City of Hope National Medical Center	Duarte	California	United States	91010
3	Stanford Cancer Center	Stanford	California	United States	94305
4	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
6	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
7	St. Francis Hospital	Greenville	South Carolina	United States	29601
8	MD Anderson Cancer Center / University of Texas	Houston	Texas	United States	77030-4000
9	Seattle Cancer Care Alliance / University of Washington Medical Center	Seattle	Washington	United States	98109
10	Christie Hospital NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
11	Southampton General Hospital	Southampton		United Kingdom	SO16 6YD