LeukemiaPhase 1NCT00126646
BL22 Immunotoxin in Treating Patients With Refractory Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, or Non-Hodgkin's Lymphoma
A Phase 1 study testing BL22 immunotoxin, antibody-drug conjugate therapy and immunotoxin therapy in people with Leukemia and Lymphoma, run by MedImmune LLC at 1 site in United States.
Trial summary
RATIONALE: BL22 immunotoxin can find tumor cells and kill them without harming normal cells. PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating patients with refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or non-Hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- BL22 immunotoxin, antibody-drug conjugate therapy and immunotoxin therapy
- Type of treatment
- Surgery or procedure
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2005to Jun 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Diagnosis of B-cell leukemia or lymphoma of 1 of the following types:
- Chronic lymphocytic leukemia
- Failed standard chemotherapy
- Prolymphocytic leukemia
- Failed standard chemotherapy
- Indolent non-Hodgkin's lymphoma, including mantle cell lymphoma
- Stage III or IV disease
- Failed ≥ 1 prior doxorubicin- or fludarabine-containing standard therapy
- CD22-positive disease, as evidenced by 1 of the following:
- More than 15% malignant cells react with anti-CD22 by immunohistochemistry
- More than 30% malignant cells are CD22-positive by fluorescence-activated cell sorting analysis
- More than 400 CD22 sites per malignant cell (average) by radiolabeled anti-CD22 binding
- Treatment is medically indicated, as evidenced by any of the following:
- Progressive disease-related symptoms
- Progressive cytopenias due to marrow involvement
- Progressive or painful splenomegaly or adenopathy
- Rapidly increasing lymphocytosis
- Autoimmune hemolytic anemia or thrombocytopenia
- Increased frequency of infections
- No neutralizing anti-toxin or anti-mouse immunoglobulin G (IgG) antibodies to BL22 or PE38
- No serum neutralization of > 75% of the activity of 1 μg/mL of BL22
- No CNS disease requiring treatment
- No hairy cell leukemia
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- More than 6 months
Hematopoietic
- Absolute neutrophil count > 1,000/mm^3*
- Platelet count > 40,000/mm^3 NOTE: *Patients with leukemia are eligible regardless of absolute neutrophil count; Grade III-IV pancytopenia or growth factor dependence allowed if due to disease
Hepatic
- Bilirubin < 1.5 times upper limit of normal (ULN)
- ALT and AST < 2.5 times ULN
Renal
- Creatinine ≤ 1.5 mg/dL
Pulmonary
- FEV1 ≥ 60% of predicted
- DLCO ≥ 55% of predicted
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior bone marrow transplantation allowed
- More than 3 weeks since prior biologic therapy, including interferon, denileukin diftitox, or LMB-2 immunotoxin
- More than 3 months since prior monoclonal antibody therapy (e.g., rituximab)
Chemotherapy
- See Disease Characteristics
- More than 3 weeks since prior cytotoxic chemotherapy
Endocrine therapy
- More than 1 week since prior steriods
- Less than 5 doses for non-treatment reasons (e.g., allergy prophylaxis)
- No evidence of disease response
Radiotherapy
- More than 3 weeks since prior whole-body electron beam radiotherapy
- Radiotherapy within the past 3 weeks allowed provided the volume of bone marrow treated is < 10% AND the patient has measurable disease located outside the radiation port
Surgery
- Not specified
Other
- More than 3 weeks since prior retinoids
- More than 3 weeks since other prior systemic therapy for this malignancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, 20892-1182
About this study
Official title: Phase I Study of BL22, A Recombinant Immunotoxin for Chronic Lymphocytic Leukemia and CD22+ Lymphomas
RATIONALE: BL22 immunotoxin can find tumor cells and kill them without harming normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating patients with refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or non-Hodgkin's lymphoma.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of recombinant BL22 immunotoxin in patients with CD22-positive refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or indolent non-Hodgkin's lymphoma.
- Determine the safety and efficacy of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the immunogenicity of this drug in these patients.
- Determine the effect of this drug on various components of the circulating cellular immune system in these patients.
OUTLINE: This is a nonrandomized, dose-escalation study. Patients are stratified according to disease type (chronic lymphocytic leukemia vs non-Hodgkin's lymphoma).
Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats ≥ every 27 days for up to 6 courses in the absence of neutralizing antibodies to BL22 or PE38, disease progression, or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients who relapse from a CR lasting ≥ 6 months may receive additional courses.
Cohorts of 3-6 patients per stratum receive escalating doses of recombinant BL22 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 24 patients (12 per stratum) will be accrued for this study within 1-2 years.
- Being tested
- BL22 immunotoxin, antibody-drug conjugate therapy, immunotoxin therapy
- Keywords
- B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, stage III marginal zone lymphoma, stage IV marginal zone lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, recurrent small lymphocytic lymphoma, stage III small lymphocytic lymphoma, stage IV small lymphocytic lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell, Lymphoma, Non-Hodgkin, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BL22 immunotoxinDrug
antibody-drug conjugate therapyProcedure or surgery
immunotoxin therapyProcedure or surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Aug 2005 (estimated)
- Study startJun 2005
- Primary completionMar 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Robert Kreitman, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00126646
- Sponsor's protocol ID
- CDR0000438672
- Other IDs
- NCI-05-C-0171, NCI-P6620, NCI-5336
- Status last verified
- Jun 2010
- First submitted
- 2 Aug 2005
- Last updated
- 22 Jun 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
Kreitman RJ, Squires DR, Stetler-Stevenson M, Noel P, FitzGerald DJ, Wilson WH, Pastan I. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. J Clin Oncol. 2005 Sep 20;23(27):6719-29. doi: 10.1200/JCO.2005.11.437. Epub 2005 Aug 1.
PubMed 16061911
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of BL22, A Recombinant Immunotoxin for Chronic Lymphocytic Leukemia and CD22+ Lymphomas
- ClinicalTrials.gov ID
- NCT00126646
- Acronym / sponsor ID
- CDR0000438672
- Keywords
- B-cell chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- Jun 2005
- Primary completion
- Mar 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 4 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: BL22 immunotoxin can find tumor cells and kill them without harming normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating patients with refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of recombinant BL22 immunotoxin in patients with CD22-positive refractory B-cell chronic lymphocytic leukemia, prolymphocytic leukemia, or indolent non-Hodgkin's lymphoma.
- Determine the safety and efficacy of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Determine the immunogenicity of this drug in these patients.
- Determine the effect of this drug on various components of the circulating cellular immune system in these patients.
OUTLINE: This is a nonrandomized, dose-escalation study. Patients are stratified according to disease type (chronic lymphocytic leukemia vs non-Hodgkin's lymphoma).
Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats ≥ every 27 days for up to 6 courses in the absence of neutralizing antibodies to BL22 or PE38, disease progression, or unacceptable toxicity. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients who relapse from a CR lasting ≥ 6 months may receive additional courses.
Cohorts of 3-6 patients per stratum receive escalating doses of recombinant BL22 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 24 patients (12 per stratum) will be accrued for this study within 1-2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BL22 immunotoxin | Drug | – |
| antibody-drug conjugate therapy | Procedure or surgery | – |
| immunotoxin therapy | Procedure or surgery | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2010.
- Results publication: PubMed 16061911Kreitman RJ, Squires DR, Stetler-Stevenson M, Noel P, FitzGerald DJ, Wilson WH, Pastan I. Phase I trial of recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) in patients with B-cell malignancies. J Clin Oncol. 2005 Sep 20;23(27):6719-29. doi: 10.1200/JCO.2005.11.437. Epub 2005 Aug 1.
- Web site for additional informationLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Kreitman, MD principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BL22 immunotoxin, antibody-drug conjugate therapy and immunotoxin therapy in people with Leukemia and Lymphoma, run by MedImmune LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00126646, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2010.