A Phase II Study Of Imtox-25 In Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma

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).

Timeline

Start

2010-09

Primary completion

2013-01

Completion

2013-01

Outcome

Outcome not reported

Stopped: “IND withdrawn”

Publications

• Background Taylor GP, Matsuoka M. Natural history of adult T-cell leukemia/lymphoma and approaches to therapy. Oncogene. 2005 Sep 5;24(39):6047-57. doi: 10.1038/sj.onc.1208979.
• Background Waldmann TA, Goldman CK, Bongiovanni KF, Sharrow SO, Davey MP, Cease KB, Greenberg SJ, Longo DL. Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac, a monoclonal antibody to the receptor for interleukin-2. Blood. 1988 Nov;72(5):1805-16.
• Background Waldmann TA, White JD, Goldman CK, Top L, Grant A, Bamford R, Roessler E, Horak ID, Zaknoen S, Kasten-Sportes C, et al. The interleukin-2 receptor: a target for monoclonal antibody treatment of human T-cell lymphotrophic virus I-induced adult T-cell leukemia. Blood. 1993 Sep 15;82(6):1701-12.
• Background Gill PS, Harrington W Jr, Kaplan MH, Ribeiro RC, Bennett JM, Liebman HA, Bernstein-Singer M, Espina BM, Cabral L, Allen S, et al. Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine. N Engl J Med. 1995 Jun 29;332(26):1744-8. doi: 10.1056/NEJM199506293322603.
• Background Thrush GR, Lark LR, Clinchy BC, Vitetta ES. Immunotoxins: an update. Annu Rev Immunol. 1996;14:49-71. doi: 10.1146/annurev.immunol.14.1.49.
• Background Ghetie V, Ghetie MA, Uhr JW, Vitetta ES. Large scale preparation of immunotoxins constructed with the Fab' fragment of IgG1 murine monoclonal antibodies and chemically deglycosylated ricin A chain. J Immunol Methods. 1988 Sep 13;112(2):267-77. doi: 10.1016/0022-1759(88)90367-5.
• Background Barth S, Schnell R, Diehl V, Engert A. Development of immunotoxins for potential clinical use in Hodgkin's disease. Ann Oncol. 1996;7 Suppl 4:135-41. doi: 10.1093/annonc/7.suppl_4.s135.
• Background Winkler U, Gottstein C, Schon G, Kapp U, Wolf J, Hansmann ML, Bohlen H, Thorpe P, Diehl V, Engert A. Successful treatment of disseminated human Hodgkin's disease in SCID mice with deglycosylated ricin A-chain immunotoxins. Blood. 1994 Jan 15;83(2):466-75.
• Background Engert A, Diehl V, Schnell R, Radszuhn A, Hatwig MT, Drillich S, Schon G, Bohlen H, Tesch H, Hansmann ML, Barth S, Schindler J, Ghetie V, Uhr J, Vitetta E. A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT-dgA) in patients with refractory Hodgkin's lymphoma. Blood. 1997 Jan 15;89(2):403-10.
• Background Schnell R, Vitetta E, Schindler J, Borchmann P, Barth S, Ghetie V, Hell K, Drillich S, Diehl V, Engert A. Treatment of refractory Hodgkin's lymphoma patients with an anti-CD25 ricin A-chain immunotoxin. Leukemia. 2000 Jan;14(1):129-35. doi: 10.1038/sj.leu.2401626.
• Background Martin PJ, Pei J, Gooley T, Anasetti C, Appelbaum FR, Deeg J, Hansen JA, Nash RA, Petersdorf EW, Storb R, Ghetie V, Schindler J, Vitetta ES. Evaluation of a CD25-specific immunotoxin for prevention of graft-versus-host disease after unrelated marrow transplantation. Biol Blood Marrow Transplant. 2004 Aug;10(8):552-60. doi: 10.1016/j.bbmt.2004.04.002.
• Background Amrolia PJ, Mucioli-Casadei G, Huls H, Heslop HE, Schindler J, Veys P, Vitetta ES, Brenner MK. Add-back of allodepleted donor T cells to improve immune reconstitution after haplo-identical stem cell transplantation. Cytotherapy. 2005;7(2):116-25. doi: 10.1080/14653240510018181.

Drugs

Indications