Clinical trial NCT01902225 (phase 1, status: completed)
Conditions: lymphoma, t-cell lymphoma, cutaneous lymphoma
ICD codes: S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S, S33.110S, S33.111S, S33.120S, S33.121S, S33.130S, S33.131S, S33.140S
Drugs: istodax, doxil
SMILES: C\C=C1/NC(=O)[C@H]2CSSCC\C=C\[C@H](CC(=O)N[C@H](C(C)C)C(=O)N2)OC(=O)[C@@H](NC1=O)C(C)C, COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O
Eligibility criteria:

        Inclusion Criteria:

          1. Able to understand and voluntarily sign an informed consent form.

          2. Age ≥18 years at the time of signing the informed consent form.

          3. Able to adhere to the study visit schedule and other protocol requirements.

          4. Biopsy-proven, measurable, Stage IB-IVB relapsed or refractory cutaneous T-cell
             lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy
             (Note: extracorporeal photopheresis will be considered a systemic therapy for this
             study)

          5. All cancer therapy, including radiation, hormonal therapy and surgery, must have been
             discontinued at least 4 weeks prior to treatment in this study. The only exceptions
             are participants with erythroderma who have been on corticosteroids for prolonged
             periods of time (>60 days) without change may continue use of either low dose systemic
             steroid (equivalent to <10 mg per day of prednisone) or low potency topical steroids
             are eligible for this study if the frequency and dosage steroids has not changed for
             60 days prior to the study. These participants should continue on the same dose of
             systemic/topical steroid throughout the study period unless they achieve a complete
             response at which time steroids can be discontinued. Patients are allowed to continue
             any medications with known activity in T cell lymphomas at the pre-enrollment doses
             for conditions other than T cell lymphomas (ie, steroids for sarcoidosis) , as long as
             there is evidence of T cell lymphoma progression while patients were on these agents.

          6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry.

          7. Laboratory test results within these ranges:

               -  Absolute neutrophil count ≥750/mm³

               -  Platelet count≥75,000/mm³

               -  Total bilirubin ≤ 2 x upper limit of normal (ULN)

               -  ULN and Aspartate Aminotransferase (ALT) (SGPT) ≤ 3 x ULN.

               -  Creatinine < 2 mg/dL

          8. Disease free of prior malignancies for ≥ 5 years with exception of currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or
             breast. Patients with early stage of prostate cancer under clinical surveillance
             without therapy are eligible

          9. Negative serum pregnancy test at the time of enrollment for females of childbearing
             potential.

         10. For males and females of child-producing potential, use of effective contraceptive
             methods during the study to include 2 methods of contraception, one being a condom.

         11. Life expectancy >90 days.

        Exclusion Criteria:

          1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          2. Pregnant or breast feeding females.

          3. Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          4. Use of any other experimental drug or therapy within 28 days of baseline except
             topical therapy for mycosis fungoides which must be discontinued 14 days prior to
             initiation of study therapy.

          5. Prior allogeneic hematopoietic cell transplant.

          6. Prior solid organ transplant.

          7. Cumulative anthracycline exposure greater than 300 mg/m2 doxorubicin equivalents.

          8. Known active viral infection with human immunodeficiency virus (HIV), hepatitis B
             virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of prior
             hepatitis B virus vaccination are eligible.

          9. Central nervous system or meningeal involvement

         10. Any known cardiac abnormalities including:

               -  Congenital long QT syndrome

               -  Baseline QTc interval ≥ 480 milliseconds;

               -  Myocardial infarction within 6 months of Cycle 1 Day 1 (C1D1). Subjects with a
                  history of myocardial infarction between 6 and 12 months prior to C1D1 who are
                  asymptomatic and have had a negative cardiac risk assessment (treadmill stress
                  test, nuclear medicine stress test, or stress echocardiogram) since the event may
                  participate

               -  Other significant ECG abnormalities including 2nd degree atrio-ventricular (AV)
                  block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50
                  beats/min)

               -  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

               -  Congestive heart failure (CHF) that meets New York Heart Association (NYHA) Class
                  II to IV definitions (see Appendix 10) and/or ejection fraction <40% by
                  Multigated Acquisition Scan (MUGA) scan or <50% by echocardiogram and/or MRI

               -  A known history of sustained ventricular tachycardia (VT), ventricular
                  fibrillation (VF), Torsade de Pointes, or cardiac arrest unless currently
                  addressed with an automatic implantable cardioverter defibrillator (AICD)

               -  Hypertrophic cardiomegaly or restrictive cardiomyopathy from prior treatment or
                  other causes

               -  Uncontrolled hypertension, i.e., blood pressure (BP) of ≥160/95; patients with 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
                  doses of beta-blockers)

               -  Any cardiac finding that is deemed ineligible at the discretion of the
                  investigator

         11. Patients taking drugs leading to significant QT prolongation and unable to stop drugs
             prior to treatment

         12. Concomitant use of CYP3A4 inhibitors or inducers unless able to stop medication(s)
             prior to starting study therapies