Immunotoxin Therapy and Cytarabine in Treating Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

This is an interventional treatment trial for Adult B Acute Lymphoblastic Leukemia Read More

Inclusion Criteria:

• Patients must have histologically confirmed B-lineage acute lymphoblastic leukemia (ALL) at diagnosis and either evidence of relapse/refractory disease based on a bone marrow/peripheral blood examination or evidence by cytogenetic studies or polymerase chain reaction (PCR) amplification; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible; patients with L3 (Burkitt's) are not eligible; for ALL in marrow or peripheral blood, immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T-cell, or mixed B/T cell); NOTE: appropriate marker studies including CD19 (B cell), CD10, CD5, and CD7 (T cell) must be performed; co-expression of myeloid antigens (CD13 and CD33) will not exclude patients; if possible, the lineage specific markers cytoplasmic CD22 or CD79a (B cells), cytoplasmic CD3 (T cells) and cytoplasmic myeloperoxidase (MPO) (myeloid cells) must be determined; patients with mixed lineage ALL (ML-ALL) as defined by a lack of cytochemical markers of myeloid differentiation, and by the presence of immunophenotypic markers suggesting both lymphoid and myeloid differentiation, are allowed
• 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
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Life expectancy of greater than 2 months
• Total bilirubin =< 1.5 x institutional upper limit of normal, unless related to leukemic infiltration or hemolysis
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal, unless related to leukemic infiltration or hemolysis
• Creatinine within normal institutional limits OR
• Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Patients 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 >= 50% by multi gated acquisition scan (MUGA) scan or echocardiogram and a corrected QT (QTc) interval of =< 450 ms for men and =< 460 ms for women
• Adequate pulmonary function defined as no evidence of dyspnea at rest
• Women of child-bearing potential and men must agree to use 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:

• Patients who have had chemotherapy or radiotherapy within 2 weeks (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
• Patients 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 a significant pleural effusion by chest x-ray
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic
• Presence of active untreated central nervous system (CNS) leukemia
• Presence of graft-versus-host disease (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 > 100 ug/ml or human ricin antibodies (HARA) > 100 ug/ml HARA after cycle 1
• Impaired liver function defined as a total bilirubin > 1.5 x normal range and AST or ALT > 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; breastfeeding should be discontinued if the mother is treated with Combotox
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible