Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

Completed · Phase 1

Conditions studied: Glioma, Hematopoietic and Lymphoid Cell Neoplasm, Lymphoma, Metastatic Malignant Solid Neoplasm, Neuroendocrine Neoplasm, Recurrent Adult Soft Tissue Sarcoma, Recurrent Bladder Carcinoma, Recurrent Breast Carcinoma, Recurrent Chronic Lymphocytic Leukemia, Recurrent Colorectal Carcinoma, Recurrent Head and Neck Carcinoma, Recurrent Lung Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Melanoma, Recurrent Pancreatic Carcinoma, Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Recurrent Prostate Carcinoma, Recurrent Renal Cell Carcinoma, Recurrent Thyroid Gland Carcinoma, Refractory Chronic Lymphocytic Leukemia, Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma, Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma, Stage III Breast Cancer AJCC v7, Stage III Colorectal Cancer AJCC v7, Stage III Cutaneous Melanoma AJCC v7, Stage III Lung Cancer AJCC v7, Stage III Pancreatic Cancer AJCC v6 and v7, Stage III Prostate Cancer AJCC v7, Stage III Renal Cell Cancer AJCC v7, Stage III Soft Tissue Sarcoma AJCC v7, Stage IIIA Breast Cancer AJCC v7, Stage IIIA Colorectal Cancer AJCC v7, Stage IIIA Cutaneous Melanoma AJCC v7, Stage IIIB Breast Cancer AJCC v7, Stage IIIB Colorectal Cancer AJCC v7, Stage IIIB Cutaneous Melanoma AJCC v7, Stage IIIC Breast Cancer AJCC v7, Stage IIIC Colorectal Cancer AJCC v7, Stage IIIC Cutaneous Melanoma AJCC v7, Stage IV Breast Cancer AJCC v6 and v7, Stage IV Colorectal Cancer AJCC v7, Stage IV Cutaneous Melanoma AJCC v6 and v7, Stage IV Lung Cancer AJCC v7, Stage IV Pancreatic Cancer AJCC v6 and v7, Stage IV Prostate Cancer AJCC v7, Stage IV Renal Cell Cancer AJCC v7, Stage IV Soft Tissue Sarcoma AJCC v7, Stage IVA Colorectal Cancer AJCC v7, Stage IVB Colorectal Cancer AJCC v7, Unresectable Solid Neoplasm

In brief

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.

Key facts

Study ID

NCT01638533

Run by

National Cancer Institute (NCI)

People needed

37

Starts

2012-08-03

Expected to finish

2020-09-01

Last updated by the study team

2025-02-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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)
• 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 and up to investigators discretion 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 inducing 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 CYP3A4

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

Where it is running

• City of Hope Comprehensive Cancer Center — Duarte, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• Emory University Hospital/Winship Cancer Institute — Atlanta, Georgia, United States
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• National Cancer Institute Developmental Therapeutics Clinic — Bethesda, Maryland, United States
• Wayne State University/Karmanos Cancer Institute — Detroit, Michigan, United States
• Mayo Clinic in Rochester — Rochester, Minnesota, United States
• Case Western Reserve University — Cleveland, Ohio, United States
• Penn State Milton S Hershey Medical Center — Hershey, Pennsylvania, United States
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States
• University Health Network-Princess Margaret Hospital — Toronto, Ontario, Canada

Full record on ClinicalTrials.gov

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