Phase 1 Study of Combotox With Cytarabine in Relapsed/Refractory B-lineage Acute Lymphoblastic Leukemia (ALL)

Inclusion Criteria:

• Must have histologically confirmed B-lineage ALL at diagnosis and either evidence of relapse / refractory disease based on a Bone Marrow / Peripheral Blood examination or evidence by cytogenetic studies or PCR amplification.
• CD19 and/or CD22 must be expressed on at least 50% of the lymphoblasts
• Disease must be refractory to conventional induction therapy or relapsed after initial standard therapy for ALL. Any number of prior therapies is permitted and including allogeneic and/or autologous stem cell transplant
• Age more than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of Combotox in combination with Cytarabine in patients less than 18 years of age, children are excluded from this study, but will be eligible for future pediatric phase 1 combination trials.
• ECOG performance status less than or equal to 2
• Life expectancy greater than 2 months
• Normal organ and marrow function as follows: total bilirubin less than 1.5 X institutional upper limit of normal, unless related to leukemic infiltration or hemolysis; AST(SGOT)/ALT(SGPT) less than 2.5 X institutional upper limit of normal, unless related to leukemic infiltration or hemolysis; Creatinine within normal institutional limits OR Creatinine clearance greater than 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
• Must have recovered from effects of prior therapy. At least 2 weeks should have elapsed since the last dose of high dose chemotherapy. Hydroxyurea, steroids and vincristine are allowed to control counts until eligibility is confirmed and study treatment can be initiated.
• Adequate cardiac function defined as an ejection fraction of more than or equal to 50% by MUGA scan or echocardiogram and a QTc interval of less than or equal to 450ms for men and less than or equal to 460ms for women
• Adequate pulmonary function defined as no evidence of dyspnea at rest.
• Use of adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• (4 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier.
• May not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to combotox or other agents used in study agents
• Presence of significant pleural effusion by chest x-ray
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic
• Presence of active untreated CNS leukemia
• Presence of GVHD more than grade 2
• History of documented seizure disorder, presence of cerebellar dysfunction, dysphasia or altered mental status on neurological examination
• Human anti-mouse antibody (HAMA) levels of 100μg/ml or human ricin antibodies (HARA) > 100μg/ml HARA after cycle 1
• Impaired liver function defined as a total bilirubin greater than 1.5 x normal range and AST or ALT greater than 2.5 x normal range unless secondary to Gilbert's disease, hemolysis or leukemic involvement of the liver
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study
• HIV-positive patients on combination antiretroviral therapy are ineligible