A phase 1 dose-escalation safety study of brentuximab vedotin in combination with multi-agent chemotherapy as frontline therapy in patients with Hodgkin lymphoma
Michelle A. Fanale
The goal of this clinical research study is to find the highest tolerable dose of brentuximab vedotin when given in combination with the chemotherapy combination Adriamycin (doxorubicin), bleomycin, vinblastine, and dacarbazine (known as ABVD) and when given combination with the chemotherapy combination Adriamycin (doxorubicin), vinblastine, and dacarbazine (known as AVD) to patients with Hodgkin lymphoma. The safety of this drug combination will also be studied.
Disease Group: Lymphoma
Treatment Agent: Adriamycin,Bleomycin,Dacarbazine,SGN-35,Vincristine
Treatment Location: Both at MD Anderson & outside MD Anderson at one or more Collaborating Sites or Institutions
Estimatated Length of Stay in Houston: N/A
Sponsor: Seattle Genetics, Inc.
Return Visit: Screening, cycle 1 day 1 and 15, Cycle 2 day 1, 15 and 28, Cycle 3-6 Day 1 and Day 15, EOT
Home Care: N/A
Primary Objectives To assess the safety profile of brentuximab vedotin (SGN-35) in combination with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and in combination with AVD (doxorubicin, vinblastine, dacarbazine) in treatment-naïve Hodgkin's Lymphoma (HL) patients with Stage IIa bulky disease or Stage IIb–IV disease To determine the maximum tolerated dose (MTD), if reached, of brentuximab vedotin administered in combination with ABVD and in combination with AVD Secondary Objectives To assess the incidence of antitherapeutic antibodies (ATA) To assess the pharmacokinetics of brentuximab vedotin when administered in combination with ABVD and when administered in combination with AVD To assess the antitumor activity of brentuximab vedotin in combination with ABVD and in combination with AVD
IRB Review and Approval Date: 03/09/2010
Recruitment Status: Not Accepting
Projected Accrual: 70
1) Treatment-naïve HL patients with Stage IIa bulky disease or Stage
2) Patients must have a histologically confirmed diagnosis of HL.
3) Patients must have bidimensional measurable disease of at least 1.5 cm as documented by radiographic technique (spiral computed tomography (CT) preferred).
4) Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status <= 2.
5) Patients must be >= 18 years and <= 60 years of age.
6) Patients must have the following required baseline laboratory data: a. Absolute neutrophil count >=1,500/microL b. Platelet count>= 75,000/microL c. Serum bilirubin level <= 1.5 x upper limit of normal (ULN) d. Serum creatinine <=1.5 x ULN e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 x ULN.
7) Females of childbearing potential must have a negative serum or urine Beta-hCG pregnancy test result within 3 days prior to the first dose of brentuximab vedotin and must agree to use an effective contraceptive method during the study and for 6 months following the last dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
8) Both females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of study drug.
9) Patients or their legally authorized representative must provide written informed consent.
1) History of another primary malignancy that has not been in remission
for at least 3 years. (The following are exempt from the 3-year limit:
nonmelanoma skin cancer, fully excised melanoma in situ [Stage 0],
curatively treated localized prostate cancer, and cervical carcinoma in
situ on biopsy or a squamous intraepithelial lesion on PAP smear).
2) Known cerebral/meningeal disease.
3) Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 45%, coronary artery disease or arrhythmias.
4) Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators.
5) Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.
6) Any active systemic viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 1 week prior to first study dose.
7) Known human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus positive status.
8) Chemotherapy, radiotherapy, biologics, and/or other treatment with immunotherapy that is not completed 4 weeks prior to study entry.
9) Women who are pregnant or lactating.
10) Patients with a known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD.
Information and next steps
Michelle A. Fanale
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