Status:
TERMINATED
Immunotoxin Therapy and Cytarabine in Treating Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
Lead Sponsor:
Albert Einstein College of Medicine
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Adult B Acute Lymphoblastic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief Summary
This phase I trial studies the side effects and the best dose of deglycosylated ricin A chain-conjugated anti-cluster of differentiation (CD)19/anti-CD22 immunotoxins when given together with cytarabi...
Detailed Description
PRIMARY OBJECTIVES: I. To define the maximum tolerated dose (MTD) of Combotox (deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins) when added to high-dose cytarabine during salv...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
April 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 26 2018
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT01408160
Start Date
April 1 2013
End Date
June 26 2018
Last Update
September 6 2019
Active Locations (2)
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1
Albert Einstein College of Medicine
The Bronx, New York, United States, 10461
2
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111