A Phase II Study Of Imtox-25 In Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma
Condition: Adult T Cell Leukemia; Adult T Cell Lymphoma
MeSH terms: Lymphoma; Leukemia; Leukemia, T-Cell; Leukemia-Lymphoma, Adult T-Cell
Intervention: IMTOX-25
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: T Cell; T-Cell; Leukemia; Lymphoma; Leukemia/Lymphoma; ATL

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).
    

Eligibility 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.