Clinical trial NCT00450944: Anti-CD19 and Anti-CD22 Immunotoxins in Treating Patients With Refractory or Relapsed B-Cell Acute Lymphoblastic Leukemia
Official title: A Phase I Study of Combination Therapy With Anti-CD19 and Anti-CD22 Immunotoxins (Combotox) in Adults With Refractory/Relapse Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Keywords: B-cell adult acute lymphoblastic leukemia
recurrent adult acute lymphoblastic leukemia
Lead sponsor: Albert Einstein College of Medicine
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-03-22
Enrollment: 10
Sex: ALL
Minimum age (years): 17
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Immunotoxins, such as anti-CD19 and anti-CD22, can find cancer cells that express CD19 and CD22 and kill them without harming normal cells. This may be an effective treatment for B-cell acute lymphoblastic leukemia.

PURPOSE: This phase I trial is studying the side effects and best dose of anti-CD19 and anti-CD22 immunotoxins in treating patients with refractory or relapsed B-cell acute lymphoblastic leukemia.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of deglycosylated ricin A chain-conjugated anti-CD19 and anti-CD22 immunotoxins (Combotox) in patients with refractory or relapsed B-cell acute lymphoblastic leukemia.
* Determine the toxicity of Combotox in these patients.
* Determine the pharmacokinetic (PK) profile of Combotox in these patients.
* Determine any antitumor activity of Combotox, in terms of the percentage of blasts in bone marrow and peripheral blood.
* Determine the levels of human antimouse and human anti-dgA antibodies in patients treated with Combotox.
* Determine if there is a correlation between PK parameters and toxicity of Combotox in these patients.
* Determine if the expression of the CD19 and CD22 cell surface antigens is affected by Combotox.

OUTLINE: This is a dose-escalation study.

Patients receive deglycosylated ricin A chain-conjugated anti-CD19 and anti-CD22 immunotoxins (Combotox) IV over 4 hours on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity.

Cohorts of patients receive escalating doses of Combotox until the maximum tolerated dose is determined.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed adult acute lymphoblastic leukemia

  * B-cell lineage
* Refractory or relapsed disease based on a bone marrow/peripheral blood examination, cytogenetic studies, or polymerase chain reaction amplification

  * Disease refractory to conventional therapy and other therapies of higher priority
* At least 50% of the blasts (in bone marrow or peripheral blood) expressing CD19 and/or CD22 by flow cytometry

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy \> 2 months
* Creatinine \< 1.5 times normal
* Bilirubin \< 1.5 times normal
* ALT or AST \< 2.5 times normal

PRIOR CONCURRENT THERAPY:

* Prior chemotherapy, biologic therapy, and/or radiotherapy allowed

Primary outcomes:
measure: Optimum dose of deglycosylated ricin A chain-conjugated anti-CD19 and anti-CD22 immunotoxins (Combotox)
measure: Efficacy of treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
state: New York
Study officials:
affiliation: Albert Einstein College of Medicine
name: Amit Verma, MD
role: STUDY_CHAIR
References: