Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction
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
18 other identifiers
interventional
37
2 countries
12
Brief Summary
This phase I trial studies the side effects and best dose of romidepsin in treating patients with lymphoma, chronic lymphocytic leukemia, or solid tumors with liver dysfunction. Romidepsin may stop the growth of cancer cells by entering the cancer cells and by blocking the activity of proteins that are important for the cancer's growth and survival.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Aug 2012
Longer than P75 for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 9, 2012
CompletedFirst Posted
Study publicly available on registry
July 11, 2012
CompletedStudy Start
First participant enrolled
August 3, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 29, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2020
CompletedFebruary 7, 2025
February 1, 2025
6.3 years
July 9, 2012
February 6, 2025
Conditions
Outcome Measures
Primary Outcomes (3)
Maximum tolerated dose 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 5.0
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).
28 days
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 5.0
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.
28 days
Pharmacokinetic (PK) profile of romidepsin in patients with varying degrees of hepatic dysfunction using liquid chromatography-electrospray ionization tandem mass spectrometric method
Pharmacokinetic 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.
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
Secondary Outcomes (2)
Child-Pugh classification of hepatic dysfunction
Baseline
Antitumor activity assessed using Response Evaluation Criteria in Solid Tumors and the International Workshop Lymphoma Response Criteria
Up to 30 days
Study Arms (1)
Treatment (romidepsin)
EXPERIMENTALPatients 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.
Interventions
Given IV
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed (at original diagnosis or subsequent recurrence or progression) lymphoma, chronic lymphocytic lymphoma (CLL) or solid tumor; patients with lymphoma or CLL must have radiologically or clinically evaluable disease, and be refractory to standard therapy as defined by relapse within 6 months of last treatment (see note below); patients with solid tumors must have radiologically or clinically evaluable disease that is metastatic, unresectable, progressive, or recurrent, and for which standard curative measures do not exist or are no longer effective
- Patients with a liver mass, raised alpha-fetoprotein level (\>= 500 ng/mL) and positive serology for hepatitis, consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of the diagnosis
- Patients with prostate cancer, renal cell cancer, neuroendocrine tumors, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are excluded in the normal and mild cohorts due to a lack of efficacy in these tumor types in phase 2 studies; patients with breast, pancreatic, bladder, head and neck cancers, as well as melanoma and other malignancies are eligible
- Note: patients with prostate cancer, renal cell cancer, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are allowed to enroll in the moderate and severe cohorts provided the patients:
- Sign a separate consent form which outlines the lack of efficacy observed in prior studies
- Are consented to the study by a protocol-specified designee who is not their longitudinal oncologist; patients with neuroendocrine tumors are still excluded from the moderate and severe cohorts
- Note: as romidepsin is approved for patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) or cutaneous T cell lymphoma (CTCL), these patients would be eligible WITHOUT the requirement of having 'relapsed within 6 months of last treatment'
- Life expectancy of \> 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Hemoglobin \>= 9 g/dL (transfusions and/or erythropoietin are permitted)
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
- Platelets \>= 100 x 10\^9/L (or platelet count \>= 30 x 10\^9 cells/L in patients with lymphoma or CLL if bone marrow disease involvement is documented)
- Creatinine =\< twice upper limit institutional normal
- Patients with abnormal liver function will be eligible and will be grouped according to the criteria below
- Group A (normal hepatic function)
- +17 more criteria
You may not qualify if:
- Patients who have had (prior to entering the study): major surgery and biologic/antibody therapies (including immunotherapies) are not permitted within 4 weeks of romidepsin administration; anti-cancer therapy including chemotherapy, radiotherapy, hormonal (with the exception of hormones for thyroid conditions), and other investigational agents will not be allowed within 14 days or five (5) half-lives (whichever is longer) prior to the first dose of romidepsin (6 weeks for nitrosoureas or mitomycin C); additionally, participants must have recovered to less than grade 2 clinically significant adverse effect(s)/toxicity(ies) of the previous therapy, with the exception of alopecia, unless approved by the principal investigator
- Patients with prostate cancer, renal cell cancer, neuroendocrine tumors, lung cancer, colorectal cancers, soft tissue sarcomas, glioma, and thyroid cancer are excluded in the normal and mild cohorts due to a lack of efficacy in these tumor types in phase 2 studies; patients with prostate cancer, renal cell cancer, lung cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer are allowed to enroll in the moderate and severe cohorts only; patients with neuroendocrine tumors are still excluded from the moderate and severe cohorts
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to romidepsin, including cyclic tetrapeptide compounds
- Concurrent medications associated with a known risk of corrected QT interval (QTc) prolongation and/or Torsades de Pointes are not allowed within 2 weeks of initiation of study treatment; those medications listed as a possible risk for causing QTc prolongation and Torsades de Pointes will be allowed, although if an alternative medication can be substituted, that would be preferable; granisetron is an acceptable antiemetic on this study, but if a patient must take ondansetron, they may NOT take any other concomitant agents which might impact their QTc
- Thiazolidinedione agents such as rosiglitazone and pioglitazone are not permitted
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with current evidence of significant cardiovascular disease (New York Heart Association class III or IV cardiac disease), symptomatic congestive heart failure, dilated/hypertrophic or restrictive cardiomyopathy, myocardial infarction (within the past 6 months), unstable angina, unstable arrhythmia or a need for anti-arrhythmic therapy (use of medications for rate control for atrial fibrillation is allowed such as calcium channel blockers and beta-blockers, if stable medication for at least last month prior to initiation of romidepsin treatment and medication not listed as causing Torsades de Pointes), or evidence of acute ischemia on electrocardiogram (ECG); marked baseline prolongation of QT/QTc interval, e.g., repeated demonstration of a QTc interval \> 450 msec\*; long QT syndrome; the required use of concomitant medication that may cause Torsades de Pointes or may cause a significant prolongation of the QTc
- Note: due to difficulties assessing QTc in patients with heart block, they may be eligible if deemed safe by a cardiologist; if a patient must take ondansetron as their antiemetic, their QTc may NOT be over 450 (no exception for patients with heart block)
- Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with this drug
- Warfarin is not permitted
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- Celgene Corporationcollaborator
Study Sites (12)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Roisin M Connolly
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 9, 2012
First Posted
July 11, 2012
Study Start
August 3, 2012
Primary Completion
November 29, 2018
Study Completion
September 1, 2020
Last Updated
February 7, 2025
Record last verified: 2025-02