Dose-Escalation Trial of Carfilzomib With and Without Romidepsin in Cutaneous T-Cell Lymphoma
Condition: Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome
MeSH terms: Mycoses; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Mycosis Fungoides; Sezary Syndrome; Lymphoma, T-Cell, Cutaneous; Syndrome; Recurrence
Intervention: carfilzomib; romidepsin; laboratory biomarker analysis
Intervention description: Given IV; Given IV; Correlative studies
Intervention MeSH terms: Romidepsin
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase I trial studies the side effects and the best dose of carfilzomib when
      given together with or without romidepsin in treating patients with stage IA-IVB cutaneous
      T-cell lymphoma. Carfilzomib and romidepsin may stop the growth of cancer cells by blocking
      some of the enzymes needed for cell growth. It is not yet known whether giving carfilzomib
      alone is more effective than when given together with romidepsin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histological confirmation of a cutaneous T-cell lymphoma (CTCL) of
             any histology; confirmation of histological diagnosis must be completed prior to
             enrollment by the lead site (Northwestern)

               -  Patients will be stratified by mycosis fungoides (MF) and Sezary syndrome (SS)
                  (report diagnostic or consistent with MF/SS), stage IA-IVB according to TNM blood
                  (TNMB) classification versus other CTCL histologies

          -  Patients must have measurable disease (using modified Severity-Weighted Assessment
             Tool [mSWAT]) and/or use of indicator lesions must be designated prior to study
             enrollment (from imaging); measurable disease upon physical exam with a negative scan
             is acceptable

          -  Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status
             of =< 2

          -  Patients must have a life expectancy of >= 3 months

          -  Patients with MF/SS must have failed at least 1 prior topical therapy (including
             steroids, nitrogen mustard, retinoids, phototherapy, photochemotherapy, radiation, and
             total skin electron beam); there is no upper limit for prior therapies

          -  Serum creatinine =< 2.0 mg/dL

          -  Total bilirubin =< 2.2 mg/dL

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2 x
             upper limit of normal (ULN)

          -  Leukocytes >= 3,000/mm^3

          -  Absolute neutrophils >= 1,500/mm^3

          -  Platelets >= 100,000/mm^3

          -  Patients must have an electrocardiogram (EKG) demonstrating QTc =< 500 ms within 28
             days prior to registration

          -  Females of child-bearing potential and sexually active males must agree to use
             effective methods of contraception:

               -  Child-bearing potential is defined as any woman (regardless of sexual
                  orientation, having undergone a tubal ligation, or remaining celibate by choice)
                  who meets the following criteria:

                    -  Has NOT undergone a hysterectomy or bilateral oophorectomy; OR

                    -  Has NOT been naturally menopausal for at least 12 consecutive months (i.e.
                       has had menses at any time in the preceding 12 consecutive months)

               -  The effectiveness of hormonal contraceptives may be reduced by romidepsin, thus
                  effective methods should include at least 1 form of barrier contraception

          -  Females of child-bearing potential must have a negative pregnancy test within 7 days
             prior to registration

          -  Patients must be disease free of any prior malignancies for >= 3 years

               -  The exception to this would be currently treated squamous cell and basal cell
                  carcinoma of the skin, carcinoma in situ of the cervix, breast, or bladder, or
                  surgically removed melanoma in situ of the skin (stage 0) with histologically
                  confirmed free margins of excision

          -  Patients must give written informed consent prior to registration on the study

        Exclusion Criteria:

          -  Patients who have received topical therapy, systemic chemotherapy, or biological
             therapy within 4 weeks prior to registration are NOT eligible for participation

          -  Patients who have undergone major surgery within 21 days prior to registration are NOT
             eligible for participation

          -  Patients who have an acute active infection requiring treatment (systemic antibiotics,
             antivirals, or antifungals) within 14 days prior to registration are NOT eligible for
             participation

          -  Patients in whom IV fluid hydration is contraindicated (e.g. due to pre-existing
             pulmonary, cardiac, or renal impairment) will NOT be eligible for participation

          -  Patients who are pregnant and/or lactating are NOT eligible for participation

          -  Patients who have had a prior stem cell transplantation are NOT eligible for
             participation

          -  Patients who have had any of the following cardiac conditions are NOT eligible for
             participation (unless otherwise noted):

               -  Unstable angina or myocardial infarction within 4 months prior to registration

               -  New York Heart Association (NYHA) class II or IV heart failure

               -  Uncontrolled angina

               -  A history of severe coronary artery disease

               -  Severe, uncontrolled ventricular arrhythmias

               -  Sick sinus syndrome

               -  Electrocardiographic evidence of acute ischemia or Grade 3 conduction system
                  abnormalities UNLESS the patient has a pacemaker

          -  Patients who exhibit uncontrolled hypertension (>= 140/90 mmHg) or uncontrolled
             diabetes within 14 days prior to registration are NOT eligible for participation

          -  Patients who have experienced significant neuropathy (grades 3-4 or grade 2 with pain)
             within 14 days prior to registration are NOT eligible for participation

          -  Patients who have a known history of allergy to Captisol (a cyclodextrin derivative
             used to stabilize carfilzomib) are NOT eligible for participation

          -  Patients who have a contraindication to any of the required concomitant drugs or
             supportive treatments (including hypersensitivity to all anticoagulation and
             antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting
             pulmonary or cardiac impairment) are NOT eligible for participation

          -  Patients with pleural effusions requiring thoracentesis or ascites requiring
             paracentesis within 14 days prior to registration are NOT eligible for participation

          -  Patients who have any serious condition, laboratory abnormality, or psychiatric
             illness that would prevent them from singing the informed consent form are NOT
             eligible for participation

          -  Patients who have had prior exposure to romidepsin or any proteasome inhibitor are NOT
             eligible for participation

          -  Patients with a known human immunodeficiency virus (HIV) infection are NOT eligible
             for participation

          -  Patients who test positive for infectious hepatitis types A, B, or C within 14 days of
             registration are NOT eligible for participation