Bortezomib and Romidepsin in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

• Status: Completed
• Trial end date: 2018-04-13
• Target enrollment: 0
• Participant gender: All

Summary

This phase I trial studies the side effects and best dose of giving bortezomib and romidepsin together in treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), indolent B-cell lymphoma, peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Bortezomib and romidepsin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Virginia Commonwealth University
• Collaborator: National Cancer Institute (NCI)
• Treatments: Bortezomib; Romidepsin

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following:

• CLL or SLL, relapsed or refractory

• Indolent B-cell lymphoma, relapsed or refractory:

• Follicle center lymphoma, follicular or diffuse

• Marginal zone B-cell lymphoma (splenic, nodal, extranodal [this includes mucosa associated lymphoid tissue (MALT)])

• Lymphoplasmacytic lymphoma

• PTCL, relapsed or refractory:

• Anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK)-positive

• Anaplastic large cell lymphoma, ALK-negative

• Angioimmunoblastic T-cell lymphoma

• Enteropathy-associated T-cell lymphoma

• Extranodal natural killer (NK)/T-cell lymphoma, nasal type

• Hepatosplenic T-cell lymphoma

• PTCL, not otherwise specified (NOS)

• Subcutaneous panniculitis-like T-cell lymphoma

• CTCL:

• CTCL with subtypes of mycosis fungoides Stage IB or higher, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma who have failed a previous systemic treatment, as per the following:

• Stage IA plaque, IB, or IIA: At least 4 prior conventional and/or experimental regimens (topical or systemic, including psoralen-ultraviolet light [PUVA] and systemic corticosteroids)

• Stage IIB, III, or IV: At least 1 prior systemic regimen (systemic corticosteroids alone or PUVA alone do not count as systemic regimens for this purpose) NOTE: Repeated use of the same regimen is considered 1 regimen

• Prior allogeneic stem cell transplant is allowed provided that all of the following conditions are met:

• >= 6 months have elapsed since allogeneic transplant

• No Graft vs. Host Disease (GVHD) is present

• Not currently on immunosuppressive therapy

• No prior or concurrent CNS malignancy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1

• ANC > 1,500/mm^3

• Platelet count > 75,000/mm^3

• Hemoglobin > 7.5 g/dL (transfusion allowed)

• Serum creatinine ≤ 1.2 mg/dL or actual or calculated creatinine clearance > 60 mL/min

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)

• Bilirubin ≤ ULN

• Serum potassium ≥ 3.5 mEq/L (supplementation allowed)

• Serum magnesium ≥ 1.7 mEq/L (supplementation allowed)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective non-hormonal contraception

• Willing and able to comply with protocol requirements

• No prior severe allergic reactions to bortezomib, boron, mannitol, or romidepsin

• No progressing toxicity secondary to bortezomib

• No grade 1 peripheral neuropathy with pain or ≥ grade 2 peripheral neuropathy by NCI-CTCAE criteria (v4.0) within the past 14 days

• No condition related to ischemic heart disease, heart failure, or the risk of torsades de pointes or sudden cardiac death, including any of the following:

• History of sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes, or resuscitated cardiac arrest unless currently addressed with an implantable cardiac defibrillator

• Baseline heart rate > 140 beats per minute

• Known congenital long QT syndrome

• QTc interval > 480 milliseconds

• Type II second-degree atrio-ventricular (AV) block, third-degree AV block, or ventricular rate < 50 beats per minute

• Myocardial infarction within the past 6 months

• Patients who have had a myocardial infarction 6-12 months ago are eligible provided they are asymptomatic and have a negative cardiac risk assessment (i.e., treadmill stress test, nuclear medicine stress test, or stress echocardiogram)

• Angina upon ordinary physical activity

• Angina only with strenuous, rapid, or prolonged exertion allowed

• ECG with evidence of cardiac ischemia, as defined by the following:

• ST depression of ≥ 2 mm, measured from isoelectric line to ST segment

• T-wave inversion ≥ 4 mm, measured from isoelectric line to peak of T-wave

• NYHA class II-IV congestive heart failure

• Known left ventricular ejection fraction < 40% by MUGA scan or < 50% by echocardiogram or MRI

• Known hypertrophic cardiomegaly or restrictive cardiomyopathy

• No uncontrolled hypertension, defined as persistent blood pressure ≥ 160/95 mm Hg despite medical management

• No clinically significant active infection, including known HIV infection or hepatitis B or C

• No other malignancy within the past 3 years except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, in situ malignancy, or curatively treated low-risk prostate cancer

• No concurrent medical condition that, in the investigator's opinion, would compromise study treatment or assessment of toxicity

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 3 weeks since prior chemotherapy, radiation therapy or investigational agents. If steroids for cancer control have been used, patients must be off theses agents for at least 1 week before starting treatment. (Maintenance therapy for non-malignant disease with prednisone or steroid equivalent dose less than 10 mg/day is permitted)

• Prior allogeneic stem cell transplantation allowed provided all of the following conditions are met:

• Greater than or equal to 6 months have elapsed since allogeneic transplant

• No Graft vs. Host Disease (GVHD) is present

• More than 4 weeks since prior bortezomib

• No concurrent oral hormonal contraceptives

• No concurrent potent or moderate CYP3A4 inhibitors

• No concurrent anti-arrhythmic agents

• No concurrent treatment with any drugs that are generally accepted to having a risk of causing torsades de pointes (class 1 drugs)

• Class 2 or 3 drugs allowed at the discretion of the investigator

• No other concurrent systemic therapy for the malignancy

• Concurrent warfarin (coumadin) allowed