Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Able to understand and voluntarily sign an informed consent form
- Age ≥ 18 at time of informed consent
- Diagnosis of one of the following:
- relapsed/refractory peripheral T-cell lymphoma of any subtype including mycosis
fungoides and Sézary syndrome of advanced stage (IIB-IVB)
**for the expansion cohort:patients must have biopsy-proven T-cell lymphoma and
measurable disease.
- relapsed/refractory DLBCL (up to 6 DLBCL patients are allowed in the
dose-escalation portion of the study)
- relapsed/refractory HL
Note: extracorporeal photopheresis is NOT considered a systemic therapy for this study.
- Transplant eligible (as determined by referring physician) patients who have failed
one prior salvage therapy or transplant ineligible (as determined by referring
physician) patients who have failed one prior therapy
- ECOG performance status of ≤ 2
- Laboratory test results within the following ranges:
- Absolute neutrophil count ≥ 1500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin ≤ 1.5 x ULN
- AST (SGOT) and ALT (SGPT) ≤ 3 x ULN
- Creatinine < 2 mg/dL
- Potassium ≥ 3.3 mmol/L or at/above the lower limit of normal for the performing
laboratory
- Magnesium ≥ 1.4 mg/dL or at/above the lower limit of normal for the performing
laboratory.
- Negative serum pregnancy test for women of childbearing potential
- Washout time of at least 4 weeks for prior biological, chemotherapeutic, or
radiotherapy
Exclusion Criteria:
- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would - in the opinion of the investigator - prevent the subject from signing the
informed consent form
- Pregnant or lactating women
- Any medical condition or laboratory abnormalities, which - in the opinion of the
investigator - places the subject at unacceptable risk, or confounds the ability to
interpret data if he/she were to participate in the study
- Positive CSF cytology during staging, symptomatic leptomeningeal involvement, or
parenchymal involvement of brain or spinal cord
- Prior allogeneic hematopoietic cell transplant
- Prior solid organ transplant
- Cirrhotic liver disease from any cause
- Known HIV infection
- Impaired cardiac function or clinically significant cardiac disease including any of
the following:
- Congenital long QT syndrome
- Screening ECG with QTc interval ≥ 500 milliseconds
- Myocardial infarction (MI) or unstable angina ≤ 6 months of C1D1; however,
subjects with a history of MI between 6 and 12 months who are asymptomatic and
have had a negative cardiac risk assessment (treadmill stress test, nuclear
medicine stress test, or stress echocardiogram) since the event would be
eligible
- Symptomatic coronary artery disease (CAD), e.g., angina Canadian Class II-IV.
In any patient in whom there is doubt, the patient should have a stress imaging
study and, if abnormal, angiography to define whether or not CAD is present
- An ECG recorded at screening showing evidence of cardiac ischemia (ST
depression of ≥2 mm, measured from isoelectric line to the ST segment). If in
any doubt, the patient should have a stress imaging study and, if abnormal,
angiography to define whether or not CAD is present
- Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV)
block type II, 3rd degree AV block, or bradycardia (defined here as ventricular
rate < 50 bpm); right bundle-branch block + left anterior hemi-block
(bifasicular block)
- Congestive heart failure (CHF) that meets New York Heart Association (NYHA)
Class II to IV definitions (see Appendix 9) and/or ejection fraction <40% by
MUGA scan or <50% by echocardiogram and/or MRI History or presence of sustained
ventricular tachycardia (VT), ventricular fibrillation (VF), torsade de
pointes, or cardiac arrest
- Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or
other causes
- Uncontrolled hypertension, i.e., blood pressure (BP) of ≥160/95; patients who
have a history of hypertension controlled by medication must be on a stable
dose (for at least one month) and meet all other inclusion criteria
- Any cardiac arrhythmia requiring an anti-arrhythmic medication, excluding
stable (i.e., at least 30 days from screening) doses of beta-blockers
- Concomitant use of drugs that may cause significant QT prolongation and/or torsades
de pointes that cannot be discontinued or switched to a different medication prior
to treatment
- Concomitant use of CYP3A4 inhibitors or inducers unless able to stop medication(s)
prior to starting study treatment
- Patients who are unwilling to stop the use of herbal remedies while receiving study
treatment
- Unable to accept blood product transfusions
- Men whose sexual partners are women of childbearing potential not using a double
method of contraception during the study and 3 months after the end of treatment.
One of these methods must be a condom
- Concurrent malignancy requiring active therapy *Patients with localized prostate
cancer having undergone surgery or radiation (field confined to ≤ 30% of
marrow-bearing bone) at least 30 days prior to study treatment are eligible