• maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) [ Time Frame: five infusions every seven days ] [ Designated as safety issue: Yes ]
  

• best overall response rate (BORR)characterize the immunogenicity, PK and PD of MDX-1411 [ Time Frame: 42 days/cycle ] [ Designated as safety issue: No ]
  

The primary objectives of this study are to determine the safety profile of MDX-1411, the maximum tolerated dose (MTD), and the dose limiting toxicity (DLT)when administered every 7 days to subjects with relapsed/refractory Chronic Lymphocytic Leukemia (CLL) or Mantle Cell Lymphoma (MCL). Secondary objectives are too determine the best overall response rate (BORR), characterize the immunogenicity of MDX-1411 and characterize the preliminary multidose pharmacokinetic profile and pharmacodynamic profile (in subjects with CLL)of MDX-1411.

Inclusion Criteria:

1. 18 years of age or older
2. Life expectancy 12 weeks or greater
3. Histologically confirmed diagnosis that is not amenable to cure by surgery or other means and has failed at least 1 prior systemic therapy
4. For MCL, measurable disease with at least 1 bidimensionally measurable lesion
5. Subjects may have been treated with up to 3 prior systemic therapies for relapsed/refractory disease or have become intolerant to a systemic therapy
6. MCL subjects with treated brain metastases must be without evidence of progression by magnetic resonance imaging (MRI) for at least 8 weeks and have discontinued steroids for at least 4 weeks prior to receiving the first dose
7. MCL subjects may have been treated with radiotherapy (RT) provided there are measurable lesions outside the field of RT
8. At least 4 weeks since the last systemic therapy, including RT, for the treatment of MCL/CLL
9. At least 4 weeks since any major surgery prior to the first dose of MDX-1411
10. At least 4 weeks since taking any corticosteroids prior to the first dose of MDX-1411
11. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1

12. Screening laboratory values must meet the following criteria:

    • WBC greater then or equal to 1500/uL
    • Neutrophils greater then or equal to 1000/uL
    • Platelets greater then or equal to 50,000/ul
    • Hemoglobin(Hb) greater then or equal to 8.0g/dL
    • Creatinine less then or equal to 1.5mg/dL or creatinine clearance (CrCl)greater then 50mL/min
    • AST less then or equal to 2.5 x ULN
    • ALT less then or equal to 2.5 x ULN
    • Alkaline phosphatase less than or equal to 2.0 x ULN
    • Bilirubin less than 1.5mg/dL ( unless diagnosed with Gilbert's syndrome)
13. No known positivity for HIV ( no laboratory testing is required), no active infection with Hepatitis B or Hepatitis C

14. Women must meet 1 of the following criteria:

    • Post-menopausal for at least 24 consecutive months; surgically incapable of bearing children ( have had a hysterectomy or bilateral oophorectomy); or utilizing a reliable form of contraception.
    • Women of child bearing potential (WCBP) must agree to use a reliable form of contraception for at least 70 days following the last dose of study drug; and
15. Men must agree to the use of male contraception during the study and for at least 180 days after the last dose of study drug.

Exclusion Criteria:

Subjects who fulfill any of the following criteria at Screening will not be eligible for admission into the study.

1. Previous treatment with any other anti-CD70 antibody
2. Any other malignancy, excluding basal or squamous cell carcinoma of the skin, cervical carcinoma in situ, or localized prostate cancer, from which the subject has not been disease-free for at least 5 years
3. Active infection (viral, bacterial, or fungal) requiring i.v. systemic therapy within 4 weeks of receiving the first dose of MDX-1411
4. Evidence of bleeding diathesis or coagulopathy
5. Active autoimmune disease requiring immunosuppressive therapy
6. Known current drug or alcohol abuse
7. Apparent active or latent tuberculosis (TB) infection (purified protein derivative test is not required) as indicated by any of the following: PPD recently converted to positive; chest x-ray with evidence of infections infiltrate
8. Women who are pregnant or nursing
9. Any underlying medical condition which, in the opinion of the Principle Investigator, will make the administration of MDX-1411 hazardous or obscure the interpretation of AE's; or
10. Psychiatric illness or social situation that would preclude study compliance. -