This phase I trial studies the side effects and best dose of yttrium Y 90 basiliximab when given together with standard combination chemotherapy before a stem cell transplant in treating patients with mature T-cell non-Hodgkin lymphoma. Radioactive substances linked to monoclonal antibodies, such as yttrium Y 90 basiliximab, can bind to cancer cells and give off radiation which may help kill cancer cells. Drugs used in chemotherapy, such as carmustine, cytarabine, etoposide, and melphalan (BEAM), 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 yttrium Y 90 basiliximab and chemotherapy before a stem cell transplant may help kill any cancer cells that are in the body and help make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Stem cells that were collected from the patient's blood and stored before treatment are later returned to the patient to replace the blood-forming cells that were destroyed.
PRIMARY OBJECTIVES: I. To determine if administration of 90Y-basiliximab/DOTA (yttrium Y 90 basiliximab), when given in combination with standard dose BEAM, as conditioning for autologous hematopoietic cell transplant (AHCT), is safe, by evaluation of toxicities, including type, frequency, severity, attribution, time course and duration. II. To determine the maximum tolerated dose (MTD) of 90Y-basiliximab/DOTA when given in combination with standard dose BEAM, in patients with T-cell non-Hodgkin lymphoma (T-NHL) as part of conditioning for AHCT. SECONDARY OBJECTIVES: I. To characterize and evaluate hematologic recovery in terms of neutrophil and platelet engraftment time. II. To estimate radiation doses to the whole body and normal organs through serial imaging studies. III. To estimate overall survival, progression-free survival, non-relapse mortality and cumulative incidence of relapse/progression at 100-days (non-relapse mortality \[NRM\] only), 1-year and 2-years. OUTLINE: This is a dose-escalation study of yttrium Y 90 basiliximab. Patients receive yttrium Y 90 basiliximab intravenously (IV) on days -21 and -14, carmustine IV over 1-2 hours on days -7 and -6, cytarabine IV twice daily (BID) on days -5 to -2, etoposide IV BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic stem cell transplant on day 0. After completion of study treatment, patients are followed up at 30, 100, and 180 days and 1, 1.5, and 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Given IV
Given IV
Given IV
Given IV
Given IV
Undergo AHCT
Correlative studies
Correlative studies
City of Hope Medical Center
Duarte, California, United States
MTD of yttrium Y 90 basiliximab defined as the highest dose in which fewer than 33% of patients experience dose limiting toxicity attributable to study treatment, among those evaluable for toxicity
Dose limiting toxicities will be graded by the Modified Bearman scale.
Time frame: 30 days post-transplant
Incidence of toxicities assessed using National Cancer Institute (NCI) CTCAE version 4.03
Observed toxicities will be summarized by type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE version 4.03 and nadir or maximum values for lab measures), date of onset, duration, reversibility, and attribution.
Time frame: Up to 100 days post-transplant
Disease response by Cheson 2007 criteria
Time frame: Up to 2 years post-transplant
Engraftment: neutrophil and platelet recovery
Time frame: Up to 2 years post-transplant
Overall survival
Survival estimates will be calculated using the Kaplan-Meier method.
Time frame: From start of therapy (stem cell infusion) to death from any cause, assessed up to 2 years post-transplant
Progression-free survival
Survival estimates will be calculated using the Kaplan-Meier method.
Time frame: From start of therapy (stem cell infusion) to the first observation of disease relapse/progression or death from any cause, assessed up to 2 years post-transplant
Non-relapse mortality
The cumulative incidence of relapse/progression and non-relapse mortality will be calculated as competing risks using the Gray method.
Time frame: From start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 2 years post-transplant
Cumulative incidence of relapse/progression
The cumulative incidence of relapse/progression and non-relapse mortality will be calculated as competing risks using the Gray method.
Time frame: From start of therapy (stem cell infusion) to the first observation of disease relapse/progression, assessed up to 2 years post-transplant
Absorbed radiation dose to organs assessed by nuclear scan images
Time frame: Up to day -14
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