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.
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.
Brief Title
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.
* 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Leukemia
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
B-cell adult acute lymphoblastic leukemia
recurrent adult acute lymphoblastic leukemia
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
120 Years
Minimum Age
17 Years
NCT Id
NCT00450944
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2005-536
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Measure
Optimum dose of deglycosylated ricin A chain-conjugated anti-CD19 and anti-CD22 immunotoxins (Combotox)
Outcome Measure
Efficacy of treatment
Secondary Ids
Secondary Id
P30CA013330
Secondary Id
AECM-CCI-2005-536
Secondary Id
AECM-CCI-05-428
Secondary Id
AECM-MMC-05-10-265C
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
120
Minimum Age Number (converted to Years and rounded down)
17
Investigators
Investigator Type
Principal Investigator
Investigator Name
Amit Verma
Investigator Email
amit.verma@einsteinmed.org
Investigator Phone
718-405-8505 / 718-904-2900