A Phase II Study of Carfilzomib in the Treatment of Relapsed/Refractory Mantle Cell Lymphoma
Condition: Lymphoma
MeSH terms: Lymphoma; Lymphoma, Mantle-Cell
Intervention: Carfilzomib
Intervention description: Starting dose: 20 mg/m2 by vein on Days 1 and 2 in Cycle 1 followed by 56 mg/m^2 for each subsequent dose thereafter) on days 1 and 2, 8 and 9, 15 and 16 of a 28-day cycle (following cycle 12 carfilzomib given on days 1 and 2 and 15 and 16 only).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoma; Mantle Cell Lymphoma; MCL; Relapsed; Refractory; Carfilzomib

Summary:

      The goal of this clinical research study is to learn if carfilzomib can help control relapsed
      or refractory MCL. The safety of this drug will also be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Confirmed diagnosis of mantle cell lymphoma.

          2. Patients must have relapsed or refractory MCL.

          3. Understand and voluntarily sign an IRB-approved informed consent form.

          4. Age >/= 18 years at the time of signing the informed consent.

          5. Patients must have bi-dimensional measurable disease (bone marrow only involvement is
             acceptable).

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

          7. Serum bilirubin <1.5 mg/dl and Creatinine Clearance >/= 30 mL/min, platelet count
             >50,000/mm^3 and absolute neutrophil count (ANC) > 1,000/mm^3. [Patients who have bone
             marrow infiltration by MCL are eligible if their ANC is ≥ 500/mm^3 (growth factor
             allowed) or their platelet level is equal to or > than 30,000/mm^3.]. AST (SGOT) and
             ALT (SGPT) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic
             metastases are present. Uric acid within normal limits.

          8. Females of childbearing potential (FCBP)* must have a negative serum or urine
             pregnancy test within 30 days of initiation of therapy. * A female of childbearing
             potential is a sexually mature woman who: 1) has not undergone a hysterectomy or
             bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24
             consecutive months (i.e., has had menses at any time in the preceding 24 consecutive
             months).

          9. FCBP must agree to use a highly-effective form of birth control while taking the study
             drug and for 1 month after the last dose of study drug. Highly-effective forms of
             birth control include implants, injectables, birth control pills with 2 hormones, some
             intrauterine devices (IUDs), or having a sterilized partner. The type of birth control
             used must be discussed with and approved by the attending physician prior to
             initiation of study drug.

         10. Males must agree to use a condom with spermicide every time they have sex during the
             study and for 3 months after the last dose of study drug. They also must agree to not
             donate sperm during the study and for 3 months after the last dose of study drug.

         11. Patients must be willing to receive transfusions of blood products.

        Exclusion Criteria:

          1. Any serious medical condition including but not limited to, uncontrolled hypertension,
             uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, chronic
             obstructive pulmonary disease (COPD), renal failure, active hemorrhage, or psychiatric
             illness that, in the investigators opinion places the patient at unacceptable risk and
             would prevent the subject from signing the informed consent form.

          2. Pregnant or breast feeding females.

          3. Known HIV infection. Patients with active hepatitis B infection (not including
             patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody).
             Known hepatitis C infection is allowed as long as there is no active disease and is
             cleared by GI consultation

          4. All patients with active central nervous system lymphoma.

          5. Significant neuropathy (Grades 3 - 4, or Grade 2 with pain) within 14 days prior to
             enrollment.

          6. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize
             carfilzomib).

          7. Contraindication to any of the required concomitant drugs or supportive treatments or
             intolerance to hydration due to preexisting pulmonary or cardiac impairment including
             pleural effusion requiring thoracentesis to ascites requiring paracentesis.

          8. Patients with active pulmonary embolism or deep vein thrombosis (diagnosed within 30
             days of study enrollment).

          9. Patients with symptomatic bradycardia (heart rate < 50 bpm, hypotension,
             light-headedness, syncope).

         10. Use of any standard/experimental anti-lymphoma drug therapy, including steroids,
             within 3 weeks of initiation of the study or use of any experimental non-drug therapy
             (e.g. donor leukocyte/mononuclear cell infusions) within 56 days of initiation of the
             study drug treatment. Prior allogeneic SCT within 16 weeks or autologous SCT within 8
             weeks of initiation of therapy.

         11. Patients with New York Health Association (NYHA) Class III and IV heart failure,
             myocardial infarction in the preceding 6 months, and conduction abnormalities,
             including but not limited to atrial fibrillation, atrioventricular (AV) block block,
             QT prolongation, sick sinus syndrome, ventricular tachycardia, as these patients may
             be at greater risk for cardiac complication, per carfilzomib labeling.

         12. The patient has a prior or concurrent malignancy that in the opinion of the
             investigator, presents a greater risk to the patient's health and survival, than of
             the MCL, within the subsequent 6 months at the time of consent. Investigator
             discretion is allowed.

         13. Acute active infection requiring treatment (systemic antibiotics, antivirals, or
             antifungals) within 14 days prior to enrollment.

         14. Patients who have received any previous Carfilzomib treatment.