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

Stopped early · Phase 1

Conditions studied: Adult B Acute Lymphoblastic Leukemia, Recurrent Adult Acute Lymphoblastic Leukemia

In brief

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 cytarabine in treating patients with B-cell acute lymphoblastic leukemia that has come back after a period of improvement (relapsed) or does not respond to treatment (refractory). Immunotoxins, such as deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins, can find certain cancer cells and kill them without harming normal cells. Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins with cytarabine may kill more cancer cells.

Key facts

Study ID: NCT01408160
Run by: Albert Einstein College of Medicine
People needed: 18
Starts: 2013-04-01
Expected to finish: 2018-06-26
Last updated by the study team: 2019-09-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

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

Where it is running

Albert Einstein College of Medicine — The Bronx, New York, United States
Fox Chase Cancer Center — Philadelphia, Pennsylvania, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.