Volasertib and Romidepsin in Treating Patients with Relapsed or Refractory Peripheral T Cell Lymphoma or Stage IIB-IV Cutaneous T Cell Lymphoma
This phase I trial studies the side effects and best dose of volasertib and romidepsin given together in treating patients with peripheral T cell lymphoma or stage IIB-IV cutaneous T cell lymphoma that has come back or does not respond to treatment. Volasertib and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Inclusion Criteria
- Patients with a relapsed/refractory peripheral T cell lymphoma; patients must have received at least one prior standard cytotoxic regimen such as cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP), or etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (EPOCH) OR
- Patients with relapsed/refractory stage IIB-IV cutaneous T cell lymphoma who have received at least one standard systemic treatment such as extracorporeal photopheresis, bexarotene, or interferon
- Eastern Cooperative Oncology Group performance status of =< 2
- Evidence of measurable or evaluable disease
- Patients must have recovered from all clinically relevant toxicities related to prior anticancer therapies to =< grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 4.03); exception to this criterion: patients with any grade of alopecia are allowed to enter the treatment
- Platelets >= 100 x 10^9/L
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x institutional upper limit of normal (ULN), except for people with liver involvement by their lymphoma, who may be included if AST/ALT =< 5 x ULN
- Total bilirubin =< 1.5 x ULN, except for patients with Gilbert’s syndrome who may be included if total bilirubin =< 3.0 x ULN and direct bilirubin =< 1.5 x ULN
- The following laboratory values must be greater than the lower limits of normal prior to starting study drug (supplementation allowed): potassium, magnesium, calcium
- Calculated or measured creatinine clearance (CrCl) > 30 ml/min
- Ability to provide written informed consent for the protocol must be obtained prior to any screening procedures; if consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures
Exclusion Criteria
- Prior treatment: * Patients must not have received chemotherapy, radiation or surgical resection of malignancy within 3 weeks prior to the start of study drug; however, if they have received nitrosourea or mitomycin C then they should not be enrolled in the study until 6 weeks after therapy was last received * No limitations to number of prior therapies * Prior treatment with volasertib or any PLK1 inhibitor * Prior treatment with a histone deacetylase inhibitor (anti-epileptics ok)
- Active, uncontrolled, serious infection, or medical, or psychiatric illness likely to interfere with participation in this clinic trial
- Known human immunodeficiency virus (HIV) infection
- Active or chronic hepatitis B infection
- Clinical evidence of symptomatic progressive brain or leptomeningeal disease during the past 6 months
- Pregnant or breast feeding
- Women and men of reproductive potential who are unwilling or unable to use an effective means of birth control during the study and for 3 months after receiving study drug
- Major surgery within the four weeks prior to initiating protocol therapy
- Diagnosis or treatment for any malignancy other than non-Hodgkin lymphoma (NHL) within the 3 years preceding day 1 of the protocol therapy; exceptions are: * Basal or squamous cell carcinoma of the skin * In situ malignancy that has been completely resected * Prostate cancer that was treated with prostatectomy or radiotherapy over 2 years before day 1 of protocol therapy as long as the prostate specific antigen (PSA) is undetectable
- Treatment with another investigational agent currently or within 21 days prior to enrollment; patients may participate in other non-treatment studies concurrently if it will not interfere with participation in this study
- Myocardial infarction or unstable angina within 6 months prior to enrollment or has New York Hospital Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Fridericia's corrected QT interval (QTcF) > 470 msec using the Fredericia formula
- Known hypersensitivity to the trial drugs (volasertib and romidepsin)
- Receiving medications that meet one of the following criteria and that cannot be discontinued at least 1 week prior to the start of treatment with study drug and for the duration of participation: * Medication with a significant known risk of prolonging the QT interval or inducing Torsades de Pointes * Strong inhibitors or strong inducers of CYP3A4/5 * Herbal supplements
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02757248.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose (MTD) of volasertib + romidepsin.
SECONDARY OBJECTIVES:
I. Evaluate the overall response rate to volasertib + romidepsin.
II. Define gene expression signals that correlate with clinical response in cutaneous T cell lymphoma (CTCL).
OUTLINE: This is a dose-escalation study.
Patients receive volasertib intravenously (IV) over 120 minutes on days 1 and 8 and romidepsin IV over 4 hours on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 4-6 weeks and every 6 months for up to 2 years.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationDuke University Medical Center
Principal InvestigatorAnne Wood Beaven
- Primary IDPro00060068
- Secondary IDsNCI-2016-01391
- ClinicalTrials.gov IDNCT02757248