- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01378871
A Phase II Study Of Imtox-25 In Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma
Phase II Study of Therapy With IMTOX-25 in Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
-
Bronx, New York, United States, 10467
- Montefiore Medical Center
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Bronx, New York, United States, 10461
- Albert Einstein Comprehensive Cancer Center
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Bronx, New York, United States, 10461
- Albert Einstein Cancer Center at Albert Einstein College of Medicine
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Bronx, New York, United States, 10461
- Albert Einstein Cancer Center
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Bronx, New York, United States, 10461
- Montefiore Medical Center
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Bronx, New York, United States, 10467
- Albert Einstein Clinical Cancer Center
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Bronx, New York, United States, 10467
- Montefiore Medical Center-
-
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age > 17 years inclusive at the time of original diagnosis of HTLV-1 associated ATL.
- Histologic verification of ATL and HTLV-1 sero-positivity at diagnosis and either evidence of relapse/refractory disease based on a Bone Marrow/Peripheral Blood examination or evidence by flow cytometry.
- Disease refractory to conventional CHOP based therapy or transplantation or deemed ineligible for salvage by transplantation.
- Presence of CD25 on at least 50% of the lymphoblasts obtained via BMA or peripheral blood as determined by flow cytometry.
- ECOG performance status 2.
- Life expectancy of > 2 months.
- Patients must have recovered from effects of prior therapy. At least 2 weeks should have elapsed since the last dose of chemotherapy (4 weeks in the case of nitrosourea-containing therapy). Steroids are considered as chemotherapy. However, if the patient has recovered from the side effects of prior therapy and has had a > 50% rise in peripheral blast count, they are immediately eligible. The 50% rise in peripheral blast count must be calculated as follows. The sample for the baseline peripheral blast count must have been taken at least 24 hours after the end of chemotherapy. The sample for the peripheral blast count that is increased by 50% of the baseline peripheral blast count may be taken at any subsequent time. A second peripheral blast count confirming the 50% rise is recommended.
- No hematopoietic limitations as patients with relapsed leukemia routinely have pancytopenia and ITs have not demonstrated hematopoietic toxicity.
- Adequate renal function defined as a serum creatinine 1.5 x normal range.
- Adequate liver function defined as a total bilirubin 1.5 x normal range and SGOT (AST) or SGPT (ALT) 1.5 x normal range.
- Adequate cardiac function defined as a shortening fraction of 27% by echocardiogram, or ejection fraction of 35-40% by MUGA scan.
- Adequate pulmonary function defined as no evidence of dyspnea at rest.
- Normal neurological exam.
- Patient and/or legal guardian must sign a written informed consent.
- All institutional, FDA, and NCI requirements for human studies must be met.
Exclusion Criteria:
- Presence of leukemic or infectious pulmonary parenchymal disease or presence of a pulmonary effusion by chest x-ray.
- Presence of CNS involvement with leukemia.
- History of documented seizure disorder or abnormal neurological examination.
- Human anti-mouse (HAMA) levels of < 1 μg/ml.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Antibody Therapy
Treatment with Imtox-25 intravenously over 4 hours every other day for 4 doses.
Hospital admission is required during this treatment.
|
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response of Imtox-25
Time Frame: 28 days
|
To determine any anti-tumor activity of Imtox-25 in relapsed/refractory ATL patients within the confines of a Phase II study as defined by overall response
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Toxicity and Affect of Treatment
Time Frame: 28 days +
|
To determine the toxicity of Imtox-25 in ATL patients To measure levels of human anti-mouse (HAMA) and human anti-dgA (HARA) antibodies. To determine whether the expression of the CD25 cell surface antigens is affected by treatment with Imtox-25 using flow cytometric analysis of lymphoblasts in peripheral blood and bone marrow |
28 days +
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Samir Parekh, MD, Montefiore Medical Center
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2009-530
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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