Ignite Creation Date:
2024-05-05 @ 11:35 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00082017
Status:
TERMINATED
Last Update Posted:
2017-05-15
First Post:
2004-04-28
Brief Title:
UCN-01 7-Hydroxystaurosporine to Treat Relapsed T-Cell Lymphomas
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Study of UCN-01 in Relapsed or Refractory Systemic Anaplastic Large Cell and Mature T-Cell Lymphomas
Status:
TERMINATED
Status Verified Date:
2017-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
IND was withdrawn by CTEP due to low accrual and cost of maintaining the IND
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 CTs 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 eg 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
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 CTs 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 eg 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
Detailed Description:
Background
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 kinase NPM-ALK
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
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 tetrameric antibody complexes TAC CD25
To evaluate mature T-cell lymphoma malignant cells by complimentary deoxyribonucleic acid 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 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 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 complimentary deoxyribonucleic acid 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
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 kinase NPM-ALK
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
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 tetrameric antibody complexes TAC CD25
To evaluate mature T-cell lymphoma malignant cells by complimentary deoxyribonucleic acid 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 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 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 complimentary deoxyribonucleic acid 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-C-0173 | None | None | None |