NCT01408160

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

A Phase 1 Study of the Deglycosylated Ricin A Chain-containing Combined Anti-CD19 and Anti-CD22 Immunotoxin Combotox in Combination With High-Dose Cytarabine in Adult Relapsed or Refractory B-lineage Acute Lymphoblastic Leukemia

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Albert Einstein College of Medicine · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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 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.

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 salvage therapy for adult patients with relapsed or refractory B-lineage acute lymphoblastic leukemia. SECONDARY OBJECTIVES: I. To evaluate the efficacy of this regimen. II. To assess for the presence of a postulated CD34+/CD38-/low/CD19+ leukemic stem cell phenotype in the bone marrow at time of relapse and to assess its association with treatment outcome. III. To determine the development of human mouse or ricin antibodies (human anti-mouse antibodies \[HAMA\]/human anti-ricin antibodies \[HARA\]). IV. To determine the pharmacokinetic characteristics of Combotox. V. To evaluate the value of fractional excretion of sodium (FeNa) as early marker of toxicity. OUTLINE: This is a dose-escalation study of deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins. Patients receive high-dose cytarabine intravenously (IV) over 2-3 hours every 12 hours on days 1-3 and deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins IV over 4 hours on days 8, 10, and 12. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 12 weeks.

Conditions

• Adult B Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Lymphoblastic Leukemia

Interventions

Type	Name	Description
DRUG	Cytarabine	Given IV
BIOLOGICAL	Deglycosylated Ricin A Chain-Conjugated Anti-CD19/Anti-CD22 Immunotoxins	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2013-04-01
• Primary completion: 2018-06-26
• Completion: 2018-06-26
• First posted: 2011-08-03
• Last updated: 2019-09-06

Locations

2 sites across 1 country: United States