E4412 A Phase I Study with an Expansion Cohort of the Combination of Ipilimumab and Brentuximab Vedotin in Patients with Relapsed/Refractory Hodgkin Lymphoma
To determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination of brentuximab vedotin and ipilimumab.
Generally health adults with relapsed or refractory classical Hodgkin Lymphoma may be eligible, with the following additional requirements: You may not have received brentuximab in the past 6 months or relapsed while on it; You may not have received other immunotherapies in the past 6 months; Women of childbearing potential may not be pregnant or breastfeeding; You must have adequate pulmonary function; You must have adequate hematology, liver, and renal function based on laboratory blood tests; You may not have or had another cancer in the last 5 years; You may not have brain or neurological involvement; You may not have autoimmune disorders or immunosuppression conditions requiring ongoing corticosteriod use; You may not have significant neuropathies; and You may not have heart failure or uncontrolled heart conditions.
Despite advances in chemotherapy, relapsed and primary refractory HL remains a significant clinical problem, with more than 1,000 primarily young lives lost annually. For these patients tumor targeting therapies alone are inadequate to induce a high complete remission rate, and are not curative. The proposed study uses a novel and unique approach of priming the peri-tumoral T cells with ipilimumab and targeting the HRS cells with CD30 specific therapy. We hypothesize that this combinatorial immuno-chemotherapy approach increasing T cell activation combined with direct targeting of HRS cells may overcome tumor cell resistance, and will deepen and prolong clinical response in patients with relapsed and refractory HL. Although the tumor microenvironment represents a significant contributor to HL biology, it has not to date been targeted to date by any directed therapy. Thus, the proposed concept is the first immuno-chemotherapy platform to target the HL tumor microenvironment in conjunction with the HRS tumor cells.
09/23/2014 04:03 AM