Expired Study
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Bethesda, Maryland 20892


Purpose:

This study will examine the effects of an experimental drug called UCN-01 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 CT scans of the chest, abdomen and pelvis. Additional tests may be done if clinically indicated, such as PET scans, bone marrow aspirations and biopsies, lumbar punctures (spinal taps) and CTs or MRI scans if there is evidence of central nervous system disease. Participants are given UNC-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.


Study summary:

Background: - UCN-01, a non-specific protein kinase C (PKC) inhibitor appears to have several mechanisms of action including PKC isoenzyme inhibition and cyclin dependent kinase activation and inhibition. - We have demonstrated that cell lines derived from T-cell lymphomas, including those with the t (2; 5) translocation, are very sensitive to UCN-01. The t (2; 5) translocation, associated with three quarters of cases of anaplastic large cell lymphomas (ALCL), is an oncogenic fusion protein - nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). - ALK is one potential target for UCN-01 action, and ALCL derived SUDHL-1 cells containing the NPM-ALK protein have been shown to be very sensitive to UCN-01. Objectives: - To assess the clinical response to UCN-01 and progression-free and overall survival in patients with relapsed or refractory systemic Anaplastic Large Cell and other mature T-cell Lymphomas. - To assess the effect of UCN-01 on ALK expression in ALCL cells. - To assess the effect of UCN-01 on soluble TAC (CD25). - To evaluate mature T-cell lymphoma malignant cells by cDNA microarray. Eligibility: - Relapsed or refractory systemic Anaplastic Large Cell Lymphoma (ALCL) with T or Null phenotype or relapsed or refractory mature T-cell lymphomas. - All patients should have evaluable or measurable disease on entry to study. - Requires systemic therapy - Performance Status ECOG less than or equal to 2 - Age 7 years or older - HIV negative - Patients should not have received systemic cytotoxic chemotherapy within 3 weeks of study entry. Design: - The study will be a Phase II study. - Patients will receive the first cycle of UCN-01 over 72 hours on days 1-3 and subsequent cycles over 36 hours. Patients with stable disease may receive UCN-01 for up to 1 year beyond achieving maximum response or stable disease, and restaging will be done every 2 cycles for the first 6 cycles and every 4 cycles thereafter. - Two sequential biopsies will be performed to investigate cDNA expression by microarray. Soluble Tac (CD25) will be serially followed in patients. - For each of the two histologies, this study will be conducted using a Simon two-stage optimal design. Up to 37 patients will be treated.


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 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, NCI. Performance Status 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 ULN (patients with elevation of total bilirubin consistent with Gilbert's disease are eligible providing they have a normal direct bilirubin); AST less than or equal to 2.5 x ULN; 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. HIV negative. Willing to use contraception and continue for at least 8 weeks following the last treatment. No active 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.


NCT ID:

NCT00082017


Primary Contact:

N/A


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States



There is no listed contact information for this specific location.

Site Status: N/A


Data Source: ClinicalTrials.gov

Date Processed: December 12, 2017

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