Phase I Study of Bortezomib and Romidepsin in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Indolent B-Cell Lymphoma, Peripheral T-Cell Lymphoma or Cutaneous T-Cell Lymphoma
Inclusion 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