Phase II Study of UCN-01 in Relapsed or Refractory Systemic Anaplastic Large Cell and Mature T-Cell Lymphomas
- UCN-01 (7-hydroxystaurosporine), a non-specific protein kinase C (PKC) inhibitor
appears to have several mechanisms of action including protein kinase C (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
- Anaplastic lymphoma receptor tyrosine kinase (ALK) is one potential target for UCN-01
action, and anaplastic large cell lymphoma (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
- To assess the effect of UCN-01 on ALK expression in ALCL cells.
- To assess the effect of UCN-01 on soluble tetrameric antibody complexes (TAC) (CD25).
- To evaluate mature T-cell lymphoma malignant cells by complimentary deoxyribonucleic
acid (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 Eastern Cooperative Oncology Group (ECOG) less than or equal to 2
- Age 7 years or older
- Human immunodeficiency virus (HIV) negative
- Patients should not have received systemic cytotoxic chemotherapy within 3 weeks of
- 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 complimentary deoxyribonucleic
acid (cDNA) expression by microarray. Soluble Tac (CD25) will be serially followed in
- 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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical Response Rate
Clinical Response Rate is the percentage of participants with a response assessed by the International Workshop to Standardize Response Criteria. Complete response (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease. Complete response unconfirmed (CRu) is per CR criteria except that if a residual node is >1.5cm, it must have regressed by >75%. Partial response (PR) is no increase in size of nodes, liver or spleen. Progressive disease (PD) is a greater than or equal to 50% increase from nadir. Details re: response criteria, see the protocol link module
Wyndham Wilson, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|