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. Subjects with ALL should have M2 or M3 bone marrow classification;
• Evidence of CD22-positive malignancy by one of the following criteria:
• > 30% of malignant cells from a disease site CD22+ by fluorescence-activated cell sorter (FACS) analysis or; -≥ 15 % of malignant cells from a disease site CD22+ by immunohistochemistry (IHC).

Stage of disease:

• Subjects must have relapsed or refractory disease and have received at least one standard chemotherapy and one salvage regimen or allogeneic stem cell transplant;
• In the view of the PI and the primary oncologist, there must be no available alternative curative therapies and subjects must either be ineligible for a hematopoietic stem cell transplant (HSCT), have refused HSCT, or have disease activity that prohibits HSCT at that time;
• Relapse after prior autologous or allogeneic HSCT is allowed. In the event of relapse after prior allogeneic HSCT, the subject must be at least 100 days post-transplant and have no evidence of ongoing active graft-vs-host disease;
• Recovered from the acute toxic effects of all prior therapy before entry.

Performance status:

• Subjects greater than or equal to 12 years of age: Eastern Cooperative Oncology Group (ECOG) score of 0, 1, 2, or 3;
• Subjects < 12 years of age: Lansky scale ¬> 50%;
• Subjects 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.

Subjects with the following CNS status, are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy:

• CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs;
• CNS 2, defined as presence of < 5/µL WBCs in CSF and cytospin positive for blasts, or > 5/µL WBCs but negative by Steinherz/Bleyer algorithm:
• CNS 2a: < 10/µL RBCs; < 5/µL WBCs and cytospin positive for blasts;
• CNS 2b: ≥ 10/µL RBCs; < 5/µL WBCs and cytospin positive for blasts;
• CNS 2c: ≥ 10/µL RBCs; ≥ 5/µL WBCs and cytospin positive for blasts but negative by Steinherz/Bleyer algorithm.

Ability to give informed consent. For subjects < 18 years old their legal guardian must give informed consent. Pediatric subjects 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 greater than or equal to 6 months and < 25 years;

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

Exclusion Criteria:

Subjects meeting any of the following criteria are not eligible for participation in the study:

- Isolated testicular or Central Nervous System (CNS) ALL;

Hepatic function:

• Inadequate liver function defined as total bilirubin > 2 × upper limit of normal (ULN) (except in the case of subjects with documented Gilbert's disease > 5 × ULN) or transaminases (ALT and AST) > 5 × ULN based on age- and laboratory-specific normal ranges;

Renal 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 less than or equal to 10,1.0] [10 < age less than or equal to 15,1.2 [> 15, 1.5]

Hematologic function:

• For non-leukemic subjects only, the absolute neutrophil count (ANC) < 1000/cmm, or platelet count < 50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (ie potentially reversible with anti-neoplastic therapy);
• A subject will not be excluded because of pancytopenia ≥ Grade 3 if it is due to disease, based on the results of bone marrow studies;

Subjects with CNS 3 disease (presence of ≥ 5/µL WBCs in CSF and cytospin positive for blasts [in the absence of a traumatic lumbar puncture] and/or clinical signs of CNS leukemia);

Radiologically-detected CNS lymphoma;

Laboratory findings consistent with Grade ≥ 3 disseminated intravascular coagulation (DIC) or any Grade 2 DIC that does not correct;

Hyperleukocytosis (≥ 50,000 blasts/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy;

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 ≤ 3 weeks prior to starting study drug;

Exceptions:

1. There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such;
2. Subjects receiving corticosteroids or hydroxyurea are allowed provided there has been no increase in dose for at least 2 weeks prior to starting study drug;
3. For radiation therapy: the volume of bone marrow treated is less than 10% and also the subject has measurable disease outside the radiation port; Other investigational agents currently or within 30 days prior to entry; Less than or equal to 1 month prior monoclonal antibody therapy (eg, rituximab).

Subjects with contraindication to corticosteroid administration;

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 subject is in remission.