UCN-01 (7-Hydroxystaurosporine) to Treat Relapsed T-Cell Lymphomas
Condition: Lymphoma, Large-Cell, Ki-1; Lymphoma, T-Cell
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Large-Cell, Anaplastic
Intervention: UCN-01 (7-hydroxystaurosporine)
Intervention description: UCN-01 for relapsed or refractory T-cell lymphomas - Cohort 1, Cycle 1: 45 mg/m^2/day continuous intravenous infusion 1 to 3 days (72 hours) for total dose of 135 mg/m^2 Cycle 2: 45 mg/m^2/day continuous intravenous infusion 1 to 2 days (36 hours) for total dose of 68 mg/m^2; Repeat cycles every 28 days.
UCN-01 for relapsed or refractory T-cell lymphomas - Cohort 2, Cycle 1: 45 mg/m^2/day continuous intravenous infusion 1 to 3 days (72 hours) for total dose of 135 mg/m^2 Cycle 2: 45 mg/m^2/day continuous intravenous infusion 1 to 2 days (36 hours) for total dose of 68 mg/m^2; Repeat cycles every 21 days.
Intervention MeSH terms: 7-hydroxystaurosporine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Protein Kinase Inhibition; Soluble Tac; Gene Expression Profiling; ALK Expression; Apoptosis; Lymphoma; Anaplastic Large Cell Lymphoma; ALCL; T-Cell Lymphoma

Summary:

      This study will examine the effects of an experimental drug called UCN-01
      (7-hydroxystaurosporine) on T-cell lymphomas. UCN-01 inhibits the growth of several different
      tumor cells, and, in laboratory studies, it has worked particularly well on tumor cells taken
      from patients with T cell lymphomas.

      Patients 9 years of age and older with T cell lymphoma that has relapsed or is not responding
      to chemotherapy may be eligible for this study. Candidates will be screened with a medical
      histories and physical examinations, blood and urine tests, electrocardiograms, chest x-rays,
      and computed tomography (CT) scans of the chest, abdomen and pelvis. Additional tests may be
      done if clinically indicated, such as positron emission tomography (PET) scans, bone marrow
      aspirations and biopsies, lumbar punctures (spinal taps) and CT's or magnetic resonance
      imaging (MRI) scans if there is evidence of central nervous system disease.

      Participants are given UCN-01 in 28-day treatment cycles. The drug is given by vein in a
      continuous 72-hour infusion on the first cycle and in 36-hour infusions on subsequent cycles.
      The total number of cycles patients receive depends on how well the tumor responds to the
      drug and how well the patient tolerates drug side effects. Patients who do well may receive
      treatment for up to 1 year. Patients whose disease worsens with treatment or who do not
      tolerate the therapy are taken off the study.

      Some or all of the screening tests are repeated periodically during the course of treatment
      to monitor safety and treatment response. X-rays and scans are done every other treatment
      cycle for the first 6 cycles and then, if the cancer is stable or improving, the interval
      between these imaging studies is lengthened to every 4 cycles. Patients whose tumors can be
      safely biopsied undergo this procedure before entering the study and 3 to 5 days after
      completing the first UCN-01 treatment. Biopsies requiring open surgery (e.g., in the chest or
      abdomen) are done only if absolutely necessary for medical care. Biopsy tissue, blood, and
      other fluids are analyzed for gene and protein studies related to lymphoma research.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Relapsed or refractory systemic Anaplastic Large Cell Lymphoma (ALCL).

        Relapsed or refractory mature T-cell lymphoma to include peripheral T-cell lymphoma
        unspecified and the following "specified" mature T-cell lymphomas:

        Adult T-cell lymphoma; Extranodal natural killer (NK)/T-cell lymphoma,

        nasal type; Enteropathy-type T-cell lymphoma;

        Hepatosplenic T-cell lymphoma;

        Subcutaneous panniculitis-like T-cell lymphoma;

        Angioimmunoblastic T-cell lymphoma.

        All patients should have evaluable or measurable disease on entry to study.

        Histology confirmed by Laboratory of Pathology, National Cancer Institute (NCI).

        Performance Status Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.

        Age 7 years or older.

        Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 50 ml/min
        for patients at least 18 years.

        Pediatric patients should have maximum serum creatinine by age as follows:

          -  Less than age 7 and less than or equal to age 10 may have a Maximum Serum Creatinine
             of 1.0 mg/dl

          -  Less than age10 and less than or equal to age 15 may have a Maximum Serum Creatinine
             of 1.2 mg/dl

          -  Age 15 years or older may have a Maximum Serum Creatinine of 1.5 mg/dl

        Alternatively, pediatric patients should have a creatinine clearance of greater than 50
        m1/min/1.73m^2.

        Total bilirubin less than 1.5 x upper limit of normal (ULN) (patients with elevation of
        total bilirubin consistent with Gilbert's disease are eligible providing they have a normal
        direct bilirubin);

        aspartate aminotransferase (AST) less than or equal to 2.5 x ULN;

        absolute neutrophil count (ANC) greater than 500/mm^3;

        and platelet greater than or equal to 50,000/mm^3;

        unless hematological impairment due to organ involvement by lymphoma.

        Provides signed informed consent.

        Not pregnant or nursing. This drug has unknown effects in pregnancy and on young
        infants/children.

        Human immunodeficiency virus (HIV) negative.

        Willing to use contraception and continue for at least 8 weeks following the last
        treatment.

        No active central nervous system (CNS) lymphoma.

        Patients should not have received systemic cytotoxic chemotherapy within 3 weeks of study
        entry.

        Have recovered from the toxic effects of prior therapy to a grade less than or equal to 1.

        No history of diabetes mellitus requiring insulin treatment.

        No symptomatic pulmonary disease.

        No evidence of symptomatic cardiac disease (e.g. symptomatic congestive heart failure,
        unstable angina pectoris, exertional angina pectoris, cardiac arrhythmia).

        Patients may not be concurrently receiving any other investigational agents.

        Not a candidate for potentially curative (i.e. transplant) treatment at the time of study
        entry or the patient has a window of opportunity to receive UCN-01 before a transplant.
        Patients are required to have considered a transplant. If, having done this, they refuse
        it, decide against it or decide to wait, they would be eligible for this study.