Track topics on Twitter Track topics that are important to you
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.
- 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.
- 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.
- 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.
- 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.
Masking: Open Label, Primary Purpose: Treatment
Lymphoma, Large-Cell, Ki-1
National Institutes of Health Clinical Center, 9000 Rockville Pike
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-08-27T03:54:25-0400
This phase II trial studies how well AT13387 works in treating patients with anaplastic large cell lymphoma, mantle cell lymphoma, or diffuse large B-cell lymphoma that has not responded t...
The goal of this clinical research study is to find the highest tolerable dose of the drug lenalidomide (Revlimid, lenalidomide) that can be given with Rituxan® (rituximab) in the treatme...
This randomized phase II trial is studying two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.
This phase II trial studies how well copanlisib and nivolumab work in treating participants with diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma that has come ba...
The main purpose of this study is to find out if it is feasible to deliver a multi-agent chemotherapy regimen which features a shorter, more intensive, immunophenotype-directed approach, a...
Diffuse large B cell lymphoma (DLBCL) is heterogeneous. We aimed to explore how tumor microenvironment promotes lymphoma cell aggressiveness and heterogeneity.
The role of consolidative radiotherapy (RT) in advanced diffuse large B-cell lymphoma (DLBCL) is not established.
To determine the spectrum of various types of lymphoma in Bahrain according to the latest World Health Organization classification criteria. Methods: A retrospective review was conducted for all ne...
B-cell lymphoid tumors that occur in association with AIDS. Patients often present with an advanced stage of disease and highly malignant subtypes including BURKITT LYMPHOMA; IMMUNOBLASTIC LARGE-CELL LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; and DIFFUSE, LARGE B-CELL, LYMPHOMA. The tumors are often disseminated in unusual extranodal sites and chromosomal abnormalities are frequently present. It is likely that polyclonal B-cell lymphoproliferation in AIDS is a complex result of EBV infection, HIV antigenic stimulation, and T-cell-dependent HIV activation.
A systemic, large-cell, non-Hodgkin, malignant lymphoma characterized by cells with pleomorphic appearance and expressing the CD30 ANTIGEN. These so-called "hallmark" cells have lobulated and indented nuclei. This lymphoma is often mistaken for metastatic carcinoma and MALIGNANT HISTIOCYTOSIS.
A group of malignant lymphomas thought to derive from peripheral T-lymphocytes in lymph nodes and other nonlymphoid sites. They include a broad spectrum of lymphocyte morphology, but in all instances express T-cell markers admixed with epithelioid histiocytes, plasma cells, and eosinophils. Although markedly similar to large-cell immunoblastic lymphoma (LYMPHOMA, LARGE-CELL, IMMUNOBLASTIC), this group's unique features warrant separate treatment.
Malignant lymphoma characterized by the presence of immunoblasts with uniformly round-to-oval nuclei, one or more prominent nucleoli, and abundant cytoplasm. This class may be subdivided into plasmacytoid and clear-cell types based on cytoplasmic characteristics. A third category, pleomorphous, may be analogous to some of the peripheral T-cell lymphomas (LYMPHOMA, T-CELL, PERIPHERAL) recorded in both the United States and Japan.
Clinically benign, histologically malignant, recurrent cutaneous T-cell lymphoproliferative disorder characterized by an infiltration of large atypical cells surrounded by inflammatory cells. The atypical cells resemble REED-STERNBERG CELLS of HODGKIN DISEASE or the malignant cells of CUTANEOUS T-CELL LYMPHOMA. In some cases, lymphomatoid papulosis progresses to lymphomatous conditions including MYCOSIS FUNGOIDES; HODGKIN DISEASE; CUTANEOUS T-CELL LYMPHOMA; or ANAPLASTIC LARGE-CELL LYMPHOMA.
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...