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.
Completed
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| deglycosylated ricin A chain-conjugated anti-CD19/anti-CD22 immunotoxins | Combination Therapy with Immunotoxins Imtox 19 Plus Imtox 22 |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Combination Therapy with Immunotoxins Imtox 19 Plus Imtox 22 | Experimental |
|
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
| Maximum Eligible Age: | 120 Years |
| Minimum Eligible Age: | 17 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Optimum dose of deglycosylated ricin A chain-conjugated anti-CD19 and anti-CD22 immunotoxins (Combotox) |
| Time Frame: | |
| Safety Issue: | |
| Description: |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Albert Einstein College of Medicine |
April 14, 2021
