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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Albert Einstein College of Medicine of Yeshiva University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov Identifier:
NCT01378871
First received: May 12, 2011
Last updated: June 22, 2011
Last verified: June 2011
  Purpose

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).


Condition Intervention Phase
Adult T Cell Leukemia
Adult T Cell Lymphoma
Drug: IMTOX-25
Other: IMTOX-25
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Therapy With IMTOX-25 in Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma

Resource links provided by NLM:


Further study details as provided by Albert Einstein College of Medicine of Yeshiva University:

Primary Outcome Measures:
  • overall response [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Toxicity and Affect of Treatment [ Time Frame: 28 days + ] [ Designated as safety issue: Yes ]

    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



Estimated Enrollment: 19
Study Start Date: December 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anitbody Therapy
Treatment with Imtox-25 intravenously over 4 hours every other day for 4 doses. Hospital admission is required during this treatment.
Drug: IMTOX-25
This agent is supplied as a sterile solution at 0.5 mg/ml. Thus a vial with 5 mls contains 2.5 mg IMTOX-25 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:
  • IMTOX-25
  • RFT5-dgA
Other: 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.
Other Name: RFT5-dgA

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01378871

Contacts
Contact: Samir Parekh, MD 718-920-4826 sparekh@montefiore.org
Contact: Dale Wyville, PA 718-430-8547 dwyville@montefiore.org

Locations
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Clinical Trials Office - Albert Einstein Cancer Center at Albe    718-904-2730    aecc@aecom.yu.edu   
Principal Investigator: Samir Parekh, MD         
Sub-Investigator: Ira Braunschweig, Md         
Sub-Investigator: Amit Verma, MD         
Albert Einstein Cancer Center at Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Clinical Trials Office - Albert Einstein Cancer Center    718-430-2302    aecc@aecom.yu.edu   
Albert Einstein Cancer Center at Albert Einstein College of Medicine Recruiting
Bronx, New York, United States, 10461
Contact: Sridhar Mani, MD    718-904-2488    smani@montefiore.org   
Albert Einstein Cancer Center Recruiting
Bronx, New York, United States, 10461
Contact: Rasim Gucalp, M.D.    718-920-4826    rgucalp@montefiore.org   
Sub-Investigator: Missak Haigentz, M.D.         
Sub-Investigator: Lakshmi Rajdev, M.D.         
Sub-Investigator: Andreas Kaubisch, M.D.         
Sub-Investigator: Sridhar Mani, M.D.         
Sub-Investigator: Roman Perez-Soler, M.D.         
Principal Investigator: Rasim Gucalp, M.D.         
Albert Einstein Cancer Center Recruiting
Bronx, New York, United States, 10461
Contact: Lakshmi Rajdev, M.D.    718-904-2588    lrajdev@montefiore.org   
Principal Investigator: Lakshmi Rajdev, M.D.         
Sub-Investigator: Roman Perez-Soler, M.D.         
Sub-Investigator: Avi Einzig, M.D.         
Sub-Investigator: Missak Haigentz, M.D.         
Albert Einstein Clinical Cancer Center Recruiting
Bronx, New York, United States, 10467
Contact: Andreas Kaubisch, MD    718-920-4826      
Albert Einstein Comprehensive Cancer Center Recruiting
Bronx, New York, United States, 10461
Contact: Rasim Ahmet Gucalp    718-920-4826      
Albert Einstein Comprehensive Cancer Center Recruiting
Bronx, New York, United States, 10461
Contact: Sridhar Mani    718-904-2488      
Montefiore Medical Center- Recruiting
Bronx, New York, United States, 10467
Contact: Lakshmi Rajdev, M.D.    718-904-2558    lrajdev@montefiore.org   
Principal Investigator: Lakshmi Rajdev, M.D.         
Sub-Investigator: Rasim Gucalp, M.D.         
Sub-Investigator: Fernando Camacho, M.D.         
Sub-Investigator: Steven Keller, M.D.         
Sub-Investigator: Missak Haigentz, M.D.         
Sub-Investigator: Roman Perez-Soler, M.D.         
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10461
Contact: Lisa M Escobar, BS    718-904-2730    lescobar@montefiore.org   
Principal Investigator: Joseph Sparano, MD         
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Rasim Gucalp, MD    718-920-4826    rgucalp@montefiore.org   
Contact: Yoko Eng, RN    718-920-2090    yeng@montefiore.org   
Sub-Investigator: Rasim Gucalp, MD         
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10461
Contact: Joseph Sparano, MD    718-904-2555    jsparano@montefiore.org   
Contact: Lisa Escobar    718-904-2730    lescobar@montefiore.org   
Principal Investigator: Mark Einstein, MD         
Sub-Investigator: Joseph Sparano, MD         
Sub-Investigator: Petra Rietschel, MD         
Sub-Investigator: Gary Goldberg, MD         
Sponsors and Collaborators
Albert Einstein College of Medicine of Yeshiva University
Investigators
Principal Investigator: Samir Parekh, MD Montefiore Medical Center
  More Information

Publications:

Responsible Party: Dr. Samir Parekh, Montefiore Medical Center
ClinicalTrials.gov Identifier: NCT01378871     History of Changes
Other Study ID Numbers: Imtox 25
Study First Received: May 12, 2011
Last Updated: June 22, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Albert Einstein College of Medicine of Yeshiva University:
T Cell
T-Cell
Leukemia
Lymphoma
Leukemia/Lymphoma
ATL

Additional relevant MeSH terms:
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, T-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on August 28, 2014