INCLUSION CRITERIA:
Patient age:
Greater than or equal to 6 months and less than 25 years.
Histologic diagnosis:
All patients must have a histologically confirmed diagnosis of acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) including lymphoblastic lymphoma, Burkitt's lymphoma, and large cell lymphoma.
CD22 expression:
1. Patients must have evidence of CD22 positivity by at least one of the following criteria:
2. Greater than 15% of malignant cells from a site react with anti-CD22 by immunohistochemistry.
3. Greater than 30% of malignant cells from a site are CD22+ by FACS analysis
Note: These criteria were employed in the phase 1 trial in adult and allow for false negative malignant cells and lower sensitivity of immunohistochemical vs. FACS analysis.
Stage of Disease and Prior Therapy:
1. Patients must have measurable or evaluable disease.
2. Patients must have relapsed or refractory disease after at least one standard chemotherapy and one salvage regimen.
3. 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.
4. Relapse after prior autologous or allogeneic BMY is allowed. In the event of relapse after prior allogeneic BMT, the patient must be at least day +100 post-transplant.
5. Patients must have had their last doses of systemic chemotherapy at least 2 weeks (6 weeks for nitrosoureas) and radiation therapy at least 3 weeks prior to starting study drug. There is no time restriction in regard to prior intrathecal chemptherapy provided there is complete recovery frrom any acute toxic effects of such.
6. Patients must have recovered from the acute toxic effects of all prior therapy before entry.
7. Patients should be off colony stimulating factors (e.g., G-CSF, GM-CSF, EPO) for at least on week prior to entry.
8. Patients receiving corticosteroids are allowed provided there has been no change in dose for at least 1 week prior to starting study drug.
9. Patients should be off other investigational agents for at least 30 days prior to entry.
Performance Status:
1. Patients greater than or equal to 12 years of age: ECOG score of 0,1,2, or 3.
2. Patients less than 12 years of age: Lansky scale greater than or equal to 40%.
3. Patients who are unable to walk because of paralysis, but who are up in a wheelchair will be considered ambulatory for the purposes of calculating the performance score.
Hematological Function:
A patient will not be excluded because of pancytopenia due to disease based on bone marrow analysis. For non-leukemia patients, the absolute neutrophil count (ANC) must be greater than 1000/mm(3) and the platelet count greater than 50,000/mm(3).
Hepatic Function:
Patients must have adequate liver function defined as total bilirubin less than 2.0 mg/dl and transaminases less than 5 x the upper limit of normal (ALT and AST) based on age- and laboratory- specific normal ranges.
Renal Function:
Patients must have an age-adjusted normal serum creatinine (see table below) OR a creatinine clearance greater than or equal to 60 mL/min/1.73m(2).
Age (Years) Maximum Serum Creatinine
(mg/dl)
less than or equal to 5 0.8
5 less than age less than or equal to 10 1.0
10 less than age less than or equal to 15 1.2
greater than 15 1.5
Patients with childbearing potential are required to practice contraception during the study.
Ability to give informed consent. For patients less than 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 greater than or equal to 17 years of age.
Durable power of attorney form completed (patients greater than or equal to 18 years of age only).
EXCLUSION CRITERIA:
CNS leukemia or lymphoma as manifested by any of the following:
1. CSF WBC greater than 5/ul and confirmation of CSF blasts.
2. Cranial neuropathies deemed secondary to underlying malignancy.
3. Radiologically detected CNS lymphoma.
NB: History of CNS involvement with no current evidence of CNS malignancy is NOT an exclusion.
Isolated testicular ALL
Clinically significant unrelated systemic illness (e.g., serious infections or significant organ dysfunction) which in the judgment of the PI would likely compromise the patient's ability to tolerate this therapy or interfere with the study procedures.
Patients whose serum neutralizes greater than 75% of the activity of 1 ug/mL of BL22 in tissue culture, due to either anti-toxin or anti-mouse-IgG antibodies.
HIV infection (due to increased risk of severe infection and unknown interaction of BL22 with antiretroviral agents).
Active hepatitis B or C infection as defined by seropositive for hepatitis B (HbSAg) or hepatitis C and elevated liver transaminases.
Patients currently receiving other investigational agents.
Lactating or pregnant females (due to unknown risk to fetus or nursing child).
High risk of inability to comply with protocol treatment as determined by PI, social work, and primary oncologist.
Warren Grant Magnuson Clinical Center (CC)