Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction
Adult Mixed Glioma
Adult Pineal Gland Astrocytoma
Adult Solid Neoplasm
AIDS Related Immunoblastic Lymphoma
AIDS-Related Burkitt Lymphoma
AIDS-Related Diffuse Large Cell Lymphoma
AIDS-Related Diffuse Mixed Cell Lymphoma
AIDS-Related Diffuse Small Cleaved Cell Lymphoma
AIDS-Related Hodgkin Lymphoma
AIDS-Related Lymphoblastic Lymphoma
AIDS-Related Primary Central Nervous System Lymphoma
Recurrent Adult Brain Neoplasm
Recurrent Adult Soft Tissue Sarcoma
Recurrent Bladder Carcinoma
Recurrent Breast Carcinoma
Recurrent Chronic Lymphocytic Leukemia
Recurrent Colorectal Carcinoma
Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma
Recurrent Head and Neck Carcinoma
Recurrent Lung Carcinoma
Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma
Recurrent Pancreatic Carcinoma
Recurrent Prostate Carcinoma
Recurrent Renal Cell Carcinoma
Recurrent Thyroid Gland Carcinoma
Refractory Chronic Lymphocytic Leukemia
Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma
Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
Other: Pharmacological Study
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 and Pharmacokinetic Single Agent Study of Romidepsin in Patients With, Lymphomas, Chronic Lymphocytic Leukemia and Select Solid Tumors and Varying Degrees of Liver Dysfunction|
- Dose-limiting toxicity of romidepsin in groups of patients with varying degree of hepatic dysfunction according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]In order to define levels of hepatic impairment at which dose modifications of romidepsin are required, data will be combined across hepatic dysfunction groups to evaluate the association between toxicity, dose, and liver assay level(s). The outcome variable, drug tolerance and dose-limiting toxicities will be modeled as function of dose and liver assay using multivariate linear regression. Higher order terms of the predictor variables and interactions will be included if there is evidence of non-linear and/or non-additive associations.
- MTD of romidepsin in groups of patients with varying degree of hepatic dysfunction according to the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]Analyses will be descriptive in nature. The observed toxicities will be characterized by dose level within each category of liver dysfunction (mild, moderate, severe, and liver transplant). These results will be summarized in relation to what is known about romidepsin in a population without liver dysfunction (as defined in this protocol).
- PK profile of romidepsin in patients with varying degrees of hepatic dysfunction using liquid chromatography-electrospray ionization tandem mass spectrometric method [ Time Frame: 0, 1, 2, 3, 4, 4.25, 4.5, 5, 6, 8, 10, 24, and 48 hours after initiation of the infusion on day 1 ] [ Designated as safety issue: No ]PK variables will be tabulated and descriptive statistics calculated for each function group. Geometric means and coefficients of variation will be presented for maximum concentration and area under the curve for each group.
- Antitumor activity assessed using Response Evaluation Criteria in Solid Tumors and the International Workshop Lymphoma Response Criteria [ Time Frame: Up to 30 days ] [ Designated as safety issue: No ]Association of antitumor activity and romidepsin treatment will be documented.
- Child-Pugh classification of hepatic dysfunction [ Time Frame: Baseline ] [ Designated as safety issue: No ]Correlations of the Child-Pugh classification of hepatic dysfunction with the observed toxicities and plasma PK of romidepsin administration will be explored.
|Study Start Date:||June 2012|
|Estimated Primary Completion Date:||September 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment (romidepsin)
Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Pharmacological Study
Correlative studiesDrug: Romidepsin
I. To establish the safety and tolerability of romidepsin given on days 1, 8, and 15 of a 28 day cycle to patients with varying degrees of liver dysfunction (mild, moderate and severe).
II. To establish the maximum tolerated dose (MTD) and appropriate dosing recommendations for romidepsin in such patients.
III. To characterize the pharmacokinetics (PK) of romidepsin in patients with varying degrees of liver dysfunction.
I. To explore correlations of the Child-Pugh classification of liver dysfunction with the observed toxicities and plasma PK of romidepsin administration.
II. To document any preliminary evidence of antitumor activity at tolerable doses of romidepsin in patients with varying degrees of liver dysfunction.
OUTLINE: This is a dose-escalation study.
Patients receive romidepsin intravenously (IV) over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01638533
|United States, California|
|City of Hope Comprehensive Cancer Center||Suspended|
|Duarte, California, United States, 91010|
|University of California Davis Comprehensive Cancer Center||Active, not recruiting|
|Sacramento, California, United States, 95817|
|City of Hope South Pasadena||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Stephen C. Koehler 626-396-2900 email@example.com|
|Principal Investigator: Stephen C. Koehler|
|United States, Georgia|
|Emory University/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Olatunji B. Alese 404-778-1868 firstname.lastname@example.org|
|Principal Investigator: Olatunji B. Alese|
|United States, Maryland|
|Johns Hopkins University/Sidney Kimmel Cancer Center||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Roisin M. Connolly 410-955-8804 email@example.com|
|Principal Investigator: Roisin M. Connolly|
|National Cancer Institute Developmental Therapeutics Clinic||Active, not recruiting|
|Bethesda, Maryland, United States, 20892|
|United States, Michigan|
|Wayne State University/Karmanos Cancer Institute||Recruiting|
|Detroit, Michigan, United States, 48201|
|Contact: Ulka N. Vaishampayan 313-576-9363|
|Principal Investigator: Ulka N. Vaishampayan|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Paul Haluska 507-284-2511 firstname.lastname@example.org|
|Principal Investigator: Paul Haluska|
|United States, Ohio|
|Case Western Reserve University||Withdrawn|
|Cleveland, Ohio, United States, 44106|
|United States, Pennsylvania|
|Penn State Milton S Hershey Medical Center||Suspended|
|Hershey, Pennsylvania, United States, 17033-0850|
|United States, Wisconsin|
|University of Wisconsin Hospital and Clinics||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Roisin M. Connolly 410-614-9217 email@example.com|
|Principal Investigator: Roisin M. Connolly|
|University Health Network-Princess Margaret Hospital||Recruiting|
|Toronto, Ontario, Canada, M5G 2M9|
|Contact: Lillian L. Siu 416-946-4501 firstname.lastname@example.org|
|Principal Investigator: Lillian L. Siu|
|Principal Investigator:||Roisin Connolly||JHU Sidney Kimmel Comprehensive Cancer Center LAO|