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
Phase 1
18 Years
N/A
18 Years
N/A
Open (Enrolling)
Both
Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatic Complications, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Male Breast Cancer, Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Bladder Cancer, Recurrent Breast Cancer, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Recurrent Lymphoepithelioma of the Nasopharynx, Recurrent Lymphoepithelioma of the Oropharynx, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Melanoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Recurrent Mucoepidermoid Carcinoma of the Oral Cavity, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Pancreatic Cancer, Recurrent Salivary Gland Cancer, Recurrent Small Lymphocytic Lymphoma, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Stage III Adenoid Cystic Carcinoma of the Oral Cavity, Stage III Basal Cell Carcinoma of the Lip, Stage III Bladder Cancer, Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage III Lymphoepithelioma of the Nasopharynx, Stage III Lymphoepithelioma of the Oropharynx, Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage III Mucoepidermoid Carcinoma of the Oral Cavity, Stage III Pancreatic Cancer, Stage III Salivary Gland Cancer, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IIIA Breast Cancer, Stage IIIA Melanoma, Stage IIIB Breast Cancer, Stage IIIB Melanoma, Stage IIIC Breast Cancer, Stage IIIC Melanoma, Stage IV Bladder Cancer, Stage IV Breast Cancer, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Melanoma, Stage IV Pancreatic Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVA Basal Cell Carcinoma of the Lip, Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVA Lymphoepithelioma of the Oropharynx, Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVA Salivary Gland Cancer, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVB Basal Cell Carcinoma of the Lip, Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVB Lymphoepithelioma of the Oropharynx, Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVB Salivary Gland Cancer, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVC Basal Cell Carcinoma of the Lip, Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVC Lymphoepithelioma of the Oropharynx, Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVC Salivary Gland Cancer, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Tongue Cancer, Waldenström Macroglobulinemia
Both
Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatic Complications, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Male Breast Cancer, Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Recurrent Adenoid Cystic Carcinoma of the Oral Cavity, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Basal Cell Carcinoma of the Lip, Recurrent Bladder Cancer, Recurrent Breast Cancer, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Recurrent Lymphoepithelioma of the Nasopharynx, Recurrent Lymphoepithelioma of the Oropharynx, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Melanoma, Recurrent Metastatic Squamous Neck Cancer With Occult Primary, Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Recurrent Mucoepidermoid Carcinoma of the Oral Cavity, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Pancreatic Cancer, Recurrent Salivary Gland Cancer, Recurrent Small Lymphocytic Lymphoma, Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Recurrent Verrucous Carcinoma of the Larynx, Recurrent Verrucous Carcinoma of the Oral Cavity, Refractory Chronic Lymphocytic Leukemia, Refractory Hairy Cell Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Stage III Adenoid Cystic Carcinoma of the Oral Cavity, Stage III Basal Cell Carcinoma of the Lip, Stage III Bladder Cancer, Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage III Lymphoepithelioma of the Nasopharynx, Stage III Lymphoepithelioma of the Oropharynx, Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage III Mucoepidermoid Carcinoma of the Oral Cavity, Stage III Pancreatic Cancer, Stage III Salivary Gland Cancer, Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage III Verrucous Carcinoma of the Larynx, Stage III Verrucous Carcinoma of the Oral Cavity, Stage IIIA Breast Cancer, Stage IIIA Melanoma, Stage IIIB Breast Cancer, Stage IIIB Melanoma, Stage IIIC Breast Cancer, Stage IIIC Melanoma, Stage IV Bladder Cancer, Stage IV Breast Cancer, Stage IV Lymphoepithelioma of the Nasopharynx, Stage IV Melanoma, Stage IV Pancreatic Cancer, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVA Basal Cell Carcinoma of the Lip, Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVA Lymphoepithelioma of the Oropharynx, Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVA Salivary Gland Cancer, Stage IVA Squamous Cell Carcinoma of the Larynx, Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVA Squamous Cell Carcinoma of the Oropharynx, Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVA Verrucous Carcinoma of the Larynx, Stage IVA Verrucous Carcinoma of the Oral Cavity, Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVB Basal Cell Carcinoma of the Lip, Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVB Lymphoepithelioma of the Oropharynx, Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVB Salivary Gland Cancer, Stage IVB Squamous Cell Carcinoma of the Larynx, Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVB Squamous Cell Carcinoma of the Oropharynx, Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVB Verrucous Carcinoma of the Larynx, Stage IVB Verrucous Carcinoma of the Oral Cavity, Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity, Stage IVC Basal Cell Carcinoma of the Lip, Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity, Stage IVC Lymphoepithelioma of the Oropharynx, Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity, Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity, Stage IVC Salivary Gland Cancer, Stage IVC Squamous Cell Carcinoma of the Larynx, Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IVC Squamous Cell Carcinoma of the Oropharynx, Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Stage IVC Verrucous Carcinoma of the Larynx, Stage IVC Verrucous Carcinoma of the Oral Cavity, T-cell Large Granular Lymphocyte Leukemia, Testicular Lymphoma, Tongue Cancer, Waldenström Macroglobulinemia
Trial Information
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
PRIMARY OBJECTIVES:
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.
SECONDARY OBJECTIVES:
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.
Inclusion Criteria:
- 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
- excluding prostate cancer, renal cell cancer, neuroendocrine tumors, lung
cancer, colorectal cancers, soft tissue sarcomas, glioma and thyroid cancer 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: As romidepsin is approved for patients with relapsed or refractory PTCL or
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 >= 75 × 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)
- Bilirubin =< upper limit of normal (ULN) and aspartate aminotransferase
(AST) =< ULN
- Group B (mild hepatic dysfunction)
- B1: bilirubin =< ULN and AST > ULN
- B2: bilirubin > ULN but =< 1.5 x ULN and any AST
- Group C (moderate hepatic dysfunction)
- Bilirubin > 1.5 x ULN to =< 3 x ULN and any AST
- Group D (severe hepatic dysfunction)
- Bilirubin > 3 x ULN but =< 10 x ULN and any AST
- Patients with active hemolysis should be excluded; no distinction will be made
between liver dysfunction due to metastases and liver dysfunction due to other
causes; registration laboratory investigations will be used to assign a patient
to a hepatic function group; liver function tests should be repeated within 24
hours prior to starting initial therapy and may result in the patients' group
assignment being altered if different to registration test results
- Patients with brain metastases who require corticosteroids or non-enzyme
anticonvulsants must be on a stable dose of corticosteroids and seizure free for 1
month prior to enrollment; patients with known brain metastases should have completed
brain irradiation (whole brain or gamma knife) more than 4 weeks before starting the
protocol; patients on enzyme inducing anticonvulsants are not eligible; note that
patients should have had their steroids tapered to low dose (i.e. < 1.5 mg of
dexamethasone/day) due to the potential for higher dexamethasone doses to induce
cytochrome P450 3A4 (CYP3A4)
- Patients with biliary obstruction for which a stent has been placed are eligible,
provided the shunt has been in place for at least 10 days prior to the first dose of
romidepsin and the liver function has stabilized; two measurements at least 2 days
apart that put the patient in the same hepatic dysfunction stratum will be accepted
as evidence of stable hepatic function; there should be no evidence of biliary sepsis
- Eligibility of patients receiving any medications or substances known to affect or
with the potential to affect the activity or PK of romidepsin will be determined
following review of their case by the site principal investigator
- Patients treated with any of the medications prohibited must discontinue their
use at least 7 days prior to the first dose of romidepsin; certain other agents
that interact with the CYP3A4 system may be used with caution
- The effects of romidepsin on the developing human fetus are unknown; for this reason
and because histone deacetylase (HDAC) inhibitors are known to be teratogenic, women
of childbearing potential and men must agree to use adequate contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately; Note: Since romidepsin binds to the estrogen receptor, the effectiveness
of estrogen containing contraceptives may be reduced
- Human immunodeficiency virus (HIV)-positive patients who are not receiving: agents
with the potential for PK interactions with romidepsin or hepatotoxic antiretrovirals
(nucleoside reverse-transcriptase inhibitors [NRTIs]: abacavir, didanosine,
emtricitabine, lamivudine, stavudine, and zidovudine), dual protease inhibitor
(PI)-based regimens except low-dose boosting with ritonavir, atazanavir, indinavir,
maraviroc, and nevirapine may be eligible; additionally, the HIV-positive patients
should have a cluster of differentiation (CD)4 count > 250/mm^3; if the specific
cause of hepatic dysfunction is unknown, the patient should be worked up for other
viral causes of hepatitis and their eligibility determined after consultation with
the principal investigator
- Patients who have received prior romidepsin use are eligible
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Patients who have had radiation, major surgery, chemotherapy, or biological therapy
within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study;
>= 2 weeks since any prior administration of study drug in an exploratory IND/Phase 0
study; patients must have recovered to at least eligibility levels due to adverse
events and/or toxicity of prior chemotherapy or biologic 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 due
to a lack of efficacy in these tumor types in phase 2 studies
- 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 risk of QTc prolongation and/or Torsades de
Pointes are not allowed within 2 weeks of initiation of study treatment; those
medications as reported but lacking substantial evidence for causing QTc prolongation
and Torsades de Pointes will be allowed, although if an alternative medication can be
substituted, that would be preferable
- Thiazolidinedione agents such as rosiglitazone and pioglitazone are not permitted due
to the cardiac risks associated with this class of agents
- 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 Points), or evidence of acute ischemia on 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
- Pregnant women are excluded from this study because romidepsin is an histone
deacetylase (HDAC) inhibitor with the potential for teratogenic or abortifacient
effects; because there is an unknown but potential risk for adverse events in nursing
infants secondary to treatment of the mother with romidepsin, breastfeeding should be
discontinued if the mother is treated with this drug
- Warfarin is not permitted due to the potential to increase international normalized
ratio (INR)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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
Outcome Description:
Analyses will be descriptive in nature in this phase I study. We will characterize observed toxicities by dose level within each category of liver dysfunction (mild, moderate, severe, and liver transplant). We will summarize these results in relation to what is known about romidepsin in a population without liver dysfunction (as defined in this protocol).
Outcome Time Frame:
28 days
Safety Issue:
Yes
Principal Investigator
Roisin Connolly
Investigator Role:
Principal Investigator
Investigator Affiliation:
Johns Hopkins University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-01040
NCT ID:
NCT01638533
Start Date:
June 2012
Completion Date:
Related Keywords:
- Adult Nasal Type Extranodal NK/T-cell Lymphoma
- Anaplastic Large Cell Lymphoma
- Angioimmunoblastic T-cell Lymphoma
- Cutaneous B-cell Non-Hodgkin Lymphoma
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
- Hepatic Complications
- Hepatosplenic T-cell Lymphoma
- Intraocular Lymphoma
- Male Breast Cancer
- Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
- Nodal Marginal Zone B-cell Lymphoma
- Noncutaneous Extranodal Lymphoma
- Peripheral T-cell Lymphoma
- Recurrent Adenoid Cystic Carcinoma of the Oral Cavity
- Recurrent Adult Burkitt Lymphoma
- Recurrent Adult Diffuse Large Cell Lymphoma
- Recurrent Adult Diffuse Mixed Cell Lymphoma
- Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
- Recurrent Adult Grade III Lymphomatoid Granulomatosis
- Recurrent Adult Hodgkin Lymphoma
- Recurrent Adult Immunoblastic Large Cell Lymphoma
- Recurrent Adult Lymphoblastic Lymphoma
- Recurrent Adult T-cell Leukemia/Lymphoma
- Recurrent Basal Cell Carcinoma of the Lip
- Recurrent Bladder Cancer
- Recurrent Breast Cancer
- Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
- Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Grade 3 Follicular Lymphoma
- Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Recurrent Lymphoepithelioma of the Nasopharynx
- Recurrent Lymphoepithelioma of the Oropharynx
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Recurrent Melanoma
- Recurrent Metastatic Squamous Neck Cancer With Occult Primary
- Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Recurrent Mucoepidermoid Carcinoma of the Oral Cavity
- Recurrent Mycosis Fungoides/Sezary Syndrome
- Recurrent Pancreatic Cancer
- Recurrent Salivary Gland Cancer
- Recurrent Small Lymphocytic Lymphoma
- Recurrent Squamous Cell Carcinoma of the Hypopharynx
- Recurrent Squamous Cell Carcinoma of the Larynx
- Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
- Recurrent Squamous Cell Carcinoma of the Nasopharynx
- Recurrent Squamous Cell Carcinoma of the Oropharynx
- Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Recurrent Verrucous Carcinoma of the Larynx
- Recurrent Verrucous Carcinoma of the Oral Cavity
- Refractory Chronic Lymphocytic Leukemia
- Refractory Hairy Cell Leukemia
- Small Intestine Lymphoma
- Splenic Marginal Zone Lymphoma
- Stage III Adenoid Cystic Carcinoma of the Oral Cavity
- Stage III Basal Cell Carcinoma of the Lip
- Stage III Bladder Cancer
- Stage III Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Stage III Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Stage III Lymphoepithelioma of the Nasopharynx
- Stage III Lymphoepithelioma of the Oropharynx
- Stage III Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Stage III Mucoepidermoid Carcinoma of the Oral Cavity
- Stage III Pancreatic Cancer
- Stage III Salivary Gland Cancer
- Stage III Squamous Cell Carcinoma of the Hypopharynx
- Stage III Squamous Cell Carcinoma of the Larynx
- Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage III Squamous Cell Carcinoma of the Nasopharynx
- Stage III Squamous Cell Carcinoma of the Oropharynx
- Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Stage III Verrucous Carcinoma of the Larynx
- Stage III Verrucous Carcinoma of the Oral Cavity
- Stage IIIA Breast Cancer
- Stage IIIA Melanoma
- Stage IIIB Breast Cancer
- Stage IIIB Melanoma
- Stage IIIC Breast Cancer
- Stage IIIC Melanoma
- Stage IV Bladder Cancer
- Stage IV Breast Cancer
- Stage IV Lymphoepithelioma of the Nasopharynx
- Stage IV Melanoma
- Stage IV Pancreatic Cancer
- Stage IV Squamous Cell Carcinoma of the Hypopharynx
- Stage IV Squamous Cell Carcinoma of the Nasopharynx
- Stage IVA Adenoid Cystic Carcinoma of the Oral Cavity
- Stage IVA Basal Cell Carcinoma of the Lip
- Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Stage IVA Lymphoepithelioma of the Oropharynx
- Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Stage IVA Mucoepidermoid Carcinoma of the Oral Cavity
- Stage IVA Salivary Gland Cancer
- Stage IVA Squamous Cell Carcinoma of the Larynx
- Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage IVA Squamous Cell Carcinoma of the Oropharynx
- Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Stage IVA Verrucous Carcinoma of the Larynx
- Stage IVA Verrucous Carcinoma of the Oral Cavity
- Stage IVB Adenoid Cystic Carcinoma of the Oral Cavity
- Stage IVB Basal Cell Carcinoma of the Lip
- Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Stage IVB Lymphoepithelioma of the Oropharynx
- Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Stage IVB Mucoepidermoid Carcinoma of the Oral Cavity
- Stage IVB Salivary Gland Cancer
- Stage IVB Squamous Cell Carcinoma of the Larynx
- Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage IVB Squamous Cell Carcinoma of the Oropharynx
- Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Stage IVB Verrucous Carcinoma of the Larynx
- Stage IVB Verrucous Carcinoma of the Oral Cavity
- Stage IVC Adenoid Cystic Carcinoma of the Oral Cavity
- Stage IVC Basal Cell Carcinoma of the Lip
- Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity
- Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity
- Stage IVC Lymphoepithelioma of the Oropharynx
- Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity
- Stage IVC Mucoepidermoid Carcinoma of the Oral Cavity
- Stage IVC Salivary Gland Cancer
- Stage IVC Squamous Cell Carcinoma of the Larynx
- Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage IVC Squamous Cell Carcinoma of the Oropharynx
- Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
- Stage IVC Verrucous Carcinoma of the Larynx
- Stage IVC Verrucous Carcinoma of the Oral Cavity
- T-cell Large Granular Lymphocyte Leukemia
- Testicular Lymphoma
- Tongue Cancer
- Waldenström Macroglobulinemia
- Urinary Bladder Neoplasms
- Breast Neoplasms
- Burkitt Lymphoma
- Carcinoma
- Carcinoma, Basal Cell
- Carcinoma, Squamous Cell
- Carcinoma, Adenoid Cystic
- Granuloma
- Hodgkin Disease
- Immunoblastic Lymphadenopathy
- Laryngeal Diseases
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Hairy Cell
- Leukemia, Lymphoid
- Leukemia, T-Cell
- Leukemia-Lymphoma, Adult T-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Non-Hodgkin
- Lymphomatoid Granulomatosis
- Waldenstrom Macroglobulinemia
- Melanoma
- Mycoses
- Mycosis Fungoides
- Pancreatic Neoplasms
- Papilloma
- Sezary Syndrome
- Lymphoma, B-Cell
- Lymphoma, Large-Cell, Immunoblastic
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, T-Cell
- Lymphoma, T-Cell, Cutaneous
- Lymphoma, T-Cell, Peripheral
- Liver Diseases
- Tongue Neoplasms
- Lymphoma, Large-Cell, Anaplastic
- Carcinoma, Mucoepidermoid
- Carcinoma, Verrucous
- Esthesioneuroblastoma, Olfactory
- Papilloma, Inverted
- Head and Neck Neoplasms
- Neoplasms, Unknown Primary
- Salivary Gland Neoplasms
- Breast Neoplasms, Male
- Lymphoma, B-Cell, Marginal Zone
- Lymphoma, Extranodal NK-T-Cell
- Hypopharyngeal Neoplasms
- Laryngeal Neoplasms
- Lymphoma, Mantle-Cell
- Paranasal Sinus Neoplasms
- Leukemia, Large Granular Lymphocytic
- Oropharyngeal Neoplasms
- Nasopharyngeal Neoplasms
Name | Location |
|---|---|
| Johns Hopkins University | Baltimore, Maryland 21205 |
| Mayo Clinic | Rochester, Minnesota 55905 |
| University of Pittsburgh Cancer Institute | Pittsburgh, Pennsylvania 15213 |
| City of Hope Medical Center | Duarte, California 91010 |
| National Institutes of Health | Bethesda, Maryland 20892 |
| Case Western Reserve University | Cleveland, Ohio 44106 |
| Wayne State University | Detroit, Michigan 48202 |
| UC Davis Comprehensive Cancer Center | Sacramento, California 95817 |
| University of Southern California | Los Angeles, California 90033 |
| Penn State Milton S Hershey Medical Center | Hershey, Pennsylvania 17033 |
| City of Hope- South Pasadena Cancer Center | South Pasadena, California 91030 |
