Clinical trial NCT01378871
Conditions: Adult T Cell Leukemia Adult T Cell Lymphoma
Keywords: T Cell T-Cell Leukemia Lymphoma Leukemia/Lymphoma ATL
Sponsor: Amit Verma
Start date: 2010-09-01; Completion date: 2013-01-01
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This clinical trial will be a multicenter phase II fixed-dose trial in which a minimum of 10 patients with immunophenotypically confirmed ATL with at least 50% of the blasts expressing CD25 as measured by flow cytometry at relapse, will receive Imtox-25. Patients are eligible for repeat courses of treatment every two weeks if they do not experience a dose limiting toxicity (DLT) as defined in Section 5.2 and do not have a HAMA/HARA level \> 1 μg/ml. The treatment will be administered in the in-patient setting. If no response is observed among the initial 9 patients, the study would be terminated early and declared negative; if at least one response is observed, accrual would continue to a total of 17 evaluable patients (total study size=19 to account for 10% of the patients being unevaluable for any reason).

Detailed description:
Adult T Cell Leukemia/Lymphoma (ATL) is a lymphoproliferative disease associated with HTLV-1 infection, characterized by circulating malignant cells expressing the IL-2 receptor (CD25). Prognosis for patients with ATL remains poor despite advances in chemotherapy, with survival in leukemic patients ranging from six months to less than one year. Novel agents that are potent and specific for the tumor cells are urgently needed to improve overall survival and decrease toxicity in this dismal disease. One therapeutic approach would be to use immunotoxins (ITs). ITs utilize a potent toxin linked to a targeting moiety designed to maximize drug delivery to the tumor cells, thus avoiding the nonspecific toxicity of conventional chemotherapeutic agents. Imtox-25 is constructed using the RFT5 murine monoclonal antibody (Mab) coupled to deglycosylated ricin-A chain (dgA) via the heterobifunctional, thiol-containing crosslinker, 4\[(succinimidyloxy) carbonyl\]-ƒÑ-methyl-ƒÑ-(2 pyridyldithio) toluene (SMPT). Phase I and II clinical studies with Imtox-25 (RFT5.dGA) have been shown safety and efficacy in adult patients with Hodgkin¡¦s disease and a recommended Phase II dose has been established.. In vitro experiments using ATL cell lines and in vivo studies in a murine xenograft model have demonstrated significant activity of Imtox-25 in this disease. Based on these results, the investigators propose to conduct a phase II trial utilizing Imtox-25 in adults with relapsed or refractory ATL.

Arms: arm 1: Treatment with Imtox-25 intravenously over 4 hours every other day for 4 doses. Hospital admission is required during this treatment.
Interventions: intervention 1: IMTOX-25
Intervention descriptions: intervention 1: This agent is supplied as a sterile solution at 0.5 mg/ml. Thus a vial with 5 mL contains 2.5 mg IMTOX-25

IMTOX-25 is an immunotoxin. It is an antibody that is bound to a piece of the poison ricin. This antibody have been shown to bind to leukemia cells and kill them because of the ricin.

15 mg/m²/cycle IV. The calculated total dose for the cycle will be divided by four and given on Days 1, 3, 5 and 7.

Protocol documents: