This phase I trial studies the side effects and best dose of radiolabeled monoclonal antibody therapy when given together with combination chemotherapy before stem cell transplant and to see how well it works in treating patients with Hodgkin lymphoma that is primary refractory (did not respond to treatment) or relapsed (returned after treatment). Radiolabeled monoclonal antibodies can find cancer cells and carry cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as carmustine, etoposide, cytarabine, 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 radiolabeled monoclonal antibody therapy together with combination chemotherapy may kill more cancer cells.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01476839.
PRIMARY OBJECTIVES:
I. To determine the safety and feasibility of the autologous hematopoietic cell transplantation (AHCT) regimen of yttrium Y-90 basiliximab/DOTA, given in combination with standard dose(s) of BEAM in patients with primary progressive or relapsed Hodgkin lymphoma (HL).
II. To determine the recommended phase II dose (RP2D) and characterize toxicities at each dose level - including time course.
III. To evaluate hematological recovery in terms of neutrophil and platelet engraftment time.
IV. To estimate overall response rate (ORR: complete remission [CR] + partial remission [PR]), response duration, overall survival, progression-free survival, and the cumulative incidence of non-relapse mortality and relapse/progression.
V. To estimate the radiation doses to the whole body and normal organs through serial imaging studies.
VI. To define biodistribution/extended pharmacokinetics of 111indium (In)-basiliximab/DOTA and 90Y- basiliximab/DOTA including terminal elimination, serum half-life (t1/2), and area under the curve (AUC).
OUTLINE: This is a dose-escalation study of yttrium Y 90 basiliximab.
DOSIMETRY STUDY: Patients receive basiliximab intravenously (IV) over 20-30 minutes and indium In 111 basiliximab IV on day -21. Patients undergo indium In 111 imaging scans daily. Patients with appropriate biodistribution continue on to treatment.
TREATMENT: Patients receive basiliximab IV over 20-30 minutes and yttrium Y 90 basiliximab IV on day -14. Patients also receive BEAM chemotherapy comprising carmustine IV over 2 hours on days -7 and -6, etoposide IV over 4 hours twice daily (BID) and cytarabine IV over 2 hours BID on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous hematopoietic progenitor cell infusion on day 0.
After completion of study treatment, patients are followed up at day 90-100, 180, 1 year, 1.5 years, and 2-5 years.
Lead OrganizationCity of Hope Comprehensive Cancer Center
Principal InvestigatorEileen Patricia Smith
