This phase I/II trial studies the side effects and best dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin, and etoposide in treating patients with Hodgkin lymphoma that has come back (relapsed) or is not responding to treatment (refractory). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving brentuximab vedotin together with an ifosfamide, carboplatin, and etoposide chemotherapy regimen may kill more cancer cells.
PRIMARY OBJECTIVES: I. To determine maximally tolerated dose of brentuximab vedotin that can be combined with ifosfamide, carboplatin and etoposide chemotherapy in patients with relapsed or refractory Hodgkin lymphoma. II. To gain a preliminary assessment of the efficacy of the above regimen. SECONDARY OBJECTIVES: I. To determine the safety and toxicity of the above regimen. II. To determine the ability to proceed to peripheral blood stem cell collection following the above regimen (the impact of above regimen on stem cell reserve). III. To assess the impact of this regimen on biomarkers from the microenvironment in Hodgkin lymphoma tumors. OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study. Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on days 1 and 8; ifosfamide IV over 24 hours and carboplatin IV over 1 hour on day 2; and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients planning to go on to consolidative high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) may undergo peripheral blood stem cell (PBSC) mobilization following the 2nd course of study therapy at the discretion of the treating physician. After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy
Will be defined as the dose at which =\< 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Time frame: Up to 28 days following the second course of chemotherapy, approximately 70 days
Percentage of Patients That Achieve a Complete Remission Following Study Treatment
Time frame: 3 weeks following the completion of chemotherapy
2 Year Overall Survival
Time frame: Up to 2 years from initiation of study therapy.
2 Year Progression-free Survival
Time frame: Up to 2 years from initiation of therapy.
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