• Estimate the maximum tolerated dose (MTD), defined as the highest dose that can be safely administered to a patient, and establish a safe dose, based on the MTD, for subsequent clinical testing. [ Time Frame: End of study ] [ Designated as safety issue: No ]
  

• To characterize the tolerability and safety profile. [ Time Frame: 30 days after last dose of study drug/per subject ] [ Designated as safety issue: Yes ]
  

To estimate the maximum tolerated dose (MTD), defined as the highest dose that can be safely administered to a patient, and to establish a safe dose, based on the MTD, for subsequent clinical testing.

Inclusion Criteria:

• Histologically confirmed diagnosis of acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) including lymphoblastic lymphoma, Burkitt's lymphoma, and large cell lymphoma
• Measurable or evaluable disease
• Evidence of CD22-positive malignancy by one of the following criteria:
• ≥ 30% of malignant cells from a disease site CD22+ by FACS analysis or
• ≥ 15 % of malignant cells from a disease site CD22+ by IHC/
• Stage of disease: Patients must have relapsed or refractory disease and have received at least one standard chemotherapy and one salvage regimen.
• In the view of the PI and the primary oncologist, there must be no available alternative curative therapies and patients must either be ineligible for a hematopoietic stem cell transplant (BMT), have refused BMT, or have disease activity that prohibits the time required to identify a suitable stem cell donor.
• Relapse after prior autologous or allogeneic BMT is allowed. In the event of relapse after prior allogeneic BMT, the patient must be at least day +100 post transplant and have no evidence of ongoing graft-vs-host disease.
• Recovered from the acute toxic effects of all prior therapy before entry.
• Performance status:
• Patients ≥ 12 years of age: ECOG score of 0, 1, 2, or 3
• Patients < 12 years of age: Lansky scale ≥ 40%
• Patients who are unable to walk because of paralysis, but who are up in a wheel chair will be considered ambulatory for the purpose of calculating the performance score.
• Ability to give informed consent. For patients <18 years old their legal guardian must give informed consent. Pediatric patients will be included in age appropriate discussion and verbal assent will be obtained for those ≥7 years of age
• Must be between the ages of ≥6 months and < 25 years

• Female and male patients with childbearing potential and their sexual partners must agree to use an approved method of contraception during the study

  • Concurrent therapy allowed with the following agents:
• Intrathecal chemotherapy
• Corticosteroids or hydroxyurea provided there has been no increase in dose for at least 2 weeks prior to starting CAT-8015

Exclusion Criteria:

• Isolated testicular ALL
• Hepatic function: Inadequate liver function defined as total bilirubin > 2.0 mg/dl OR transaminases > 5x the upper limit of normal (ALT and AST) based on age- and laboratory- specific normal ranges
• Renal function: With greater than age-adjusted normal serum creatinine enal function: With greater than age-adjusted normal serum creatinine (see Table below) AND a creatinine clearance <60 mL/min/1.73 m2.

Age(Years) Maximum Serum Creatinine (mg/dl) [< 5 0.8] [5 < age < 10 1.0] [10 < age < 15 1.2] [> 15 1.5]

• Hematologic function:

• For non-leukemic patients only, the ANC < 1000/cmm, or platelet count

  ≤50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy)

• A patient will not be excluded because of pancytopenia ≥ Grade 3 if it is due to disease, based on the results of bone marrow studies
• Central Nervous System (CNS) involvement by tumor (History of CNS involvement is not an exclusion criterion); CNS leukemia or lymphoma as manifested by any of the following:
• CSF WBC >5/µl and confirmation of CSF blasts
• Cranial neuropathies deemed secondary to underlying malignancy
• Radiologically detected CNS lymphoma.
• Pregnant or breast-feeding females
• Prior treatment with CAT-3888 (BL22) or any pseudomonas-exotoxin-containing compound.
• Recent prior therapy:
• Systemic chemotherapy ≤2 weeks (6 weeks for nitrosoureas) and radiation therapy at ≤ 3 weeks prior to starting study drug(with some exceptions, specified in the protocol).
• Other investigational agents currently or within 30 days prior to entry.
• Less than or equal to 1 month prior monoclonal antibody therapy (e.g. rituximab)
• HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs)
• Active hepatitis B or C infection as defined by seropositive for hepatitis B (HBsAg) or hepatitis C and elevated liver transaminases
• Uncontrolled, symptomatic, intercurrent illness including but not limited to: infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements.
• Second malignancy other than non-basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and patient is in remission.