LeukemiaPhase 1NCT00077493
BL22 Immunotoxin In Treating Young Patients With Relapsed or Refractory Acute Lymphoblastic 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 locate tumor cells and kill them without harming normal cells. BL22 immunotoxin may be effective in treating relapsed or refractory acute lymphoblastic leukemia and non-Hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages 6 months to 24 years
- What is being tested?
- BL22 immunotoxin, antibody-drug conjugate therapy and immunotoxin therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Oct 2008
- 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 6 months to 24 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS:
- Histologically confirmed acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (including lymphoblastic lymphoma, Burkitt's lymphoma, and large cell lymphoma)
- Not amenable to available curative therapies
- Relapsed or refractory disease after at least 1 standard chemotherapy and 1 salvage regimen
- CD22 positive according to at least 1 of the following criteria:
- More than 15% CD22-positive malignant cells by immunohistochemistry
- More than 30% CD22-positive malignant cells by fluorescent-activated cell sorter analysis
- Measurable or evaluable disease
- Prior CNS involvement allowed provided there is no current evidence of CNS malignancy
- No CNS leukemia or lymphoma as manifested by any of the following:
- Cerebrospinal fluid (CSF) WBC ≥ 5/mm^3 and confirmation of CSF blasts
- Cranial neuropathies secondary to underlying malignancy
- Radiologically detected CNS lymphoma
- No isolated testicular ALL
- Ineligible for or refused hematopoietic stem cell transplantation OR has disease activity that prohibits the time required to identify a suitable stem cell donor
PATIENT CHARACTERISTICS:
Age
- 6 months to 24 years
Performance status
- ECOG 0-3 (12 to 24 years of age)
- Lansky 40-100% (under 12 years of age)
Life expectancy
- Not specified
Hematopoietic
- See Disease Characteristics
- Absolute neutrophil count > 1,000/mm^3 *
- Platelet count > 50,000/mm^3 * NOTE: *Non-leukemic patients only
Hepatic
- Bilirubin ≤ 2.0 mg/dL
- AST and ALT ≤ 5 times upper limit of normal
- No active hepatitis B or C infection
Renal
- Creatinine normal for age OR
- Creatinine clearance ≥ 60 mL/min
Immunologic
- No serum neutralization of more than 75% of the activity of 1 µg/mL of study drug
- HIV negative
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No clinically significant unrelated systemic illness that would preclude study participation
- No other significant organ dysfunction that would preclude study participation
- No psychiatric illness or social situation that would preclude study compliance
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
- Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT) allowed
- More than 100 days since prior allogeneic HSCT
Chemotherapy
- See Disease Characteristics
- At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas)
Endocrine therapy
- Concurrent corticosteroids allowed provided there has been no increase in the dose 1 week prior to and after study entry
- Steroid taper allowed
Radiotherapy
- At least 3 weeks since prior radiotherapy
- Allowed in the past 3 weeks provided the volume of the bone marrow treated is < 10% AND the patients has measurable disease outside of the radiation port
Surgery
- Not specified
Other
- Recovered from prior therapy
- At least 30 days since prior investigational drugs
- No other concurrent investigational drugs
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: Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas
RATIONALE: BL22 immunotoxin can locate tumor cells and kill them without harming normal cells. BL22 immunotoxin may be effective in treating relapsed or refractory acute lymphoblastic leukemia and non-Hodgkin's lymphoma.
PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating young patients with relapsed or refractory acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the toxic effects of BL22 immunotoxin in pediatric patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
- Determine the maximum tolerated dose of this drug in these patients.
- Determine the immunogenicity of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
Secondary
- Determine the in vitro cytotoxicity of this drug against lymphoblasts from patients with acute lymphoblastic leukemia.
- Determine the therapeutic efficacy of this drug in inducing remissions in these patients.
- Determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug.
OUTLINE: This is a non-randomized, dose-escalation study.
Patients receive BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses.
Cohorts of 3-6 patients receive escalating doses of 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. Once the MTD is determined, the cohort is expanded and a total of 12 patients are treated at that dose.
Patients are followed weekly for at least 1 month and then every 1-3 months thereafter.
PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study.
- Being tested
- BL22 immunotoxin, antibody-drug conjugate therapy, immunotoxin therapy, monoclonal antibody therapy
- Keywords
- recurrent childhood acute lymphoblastic leukemia, Burkitt lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, childhood non-Hodgkin lymphoma
- Medical subject headings
- Leukemia, Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Dendritic Cell Sarcoma, Interdigitating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BL22 immunotoxinDrug
BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses.
antibody-drug conjugate therapyProcedure or surgery
CD22 antibody, RFB4 on day 7
immunotoxin therapyProcedure or surgery
tested for immunogenicity to CAT-8015 before each cycle and at end of study.
monoclonal antibody therapyProcedure or surgery
administered intravenously over 30 minutes.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | BL22 immunotoxin Receives: Drug: BL22 immunotoxin |
| 2 | Active comparator | antibody therapy Receives: Procedure: antibody-drug conjugate therapy |
| 3 | Active comparator | immunotoxin therapy Receives: Procedure: immunotoxin therapy |
| 4 | Active comparator | monoclonal antibody therapy Receives: Procedure: monoclonal antibody therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
assessment of efficacy, safety, pharmacokinetics, immunogenicity.
Measured: end of study
Secondary outcomes (1)
Expansion of MTD
Measured: end of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2004 (estimated)
- Study startJan 2004
- Primary completionOct 2008 (estimated)
- Study completionOct 2008 (estimated)
Why it stopped: protocol development and Amended protocol revision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 95 participants (estimated)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cambridge Antibody Technology
- Investigators
- Alan S. Wayne, MD, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00077493
- Sponsor's protocol ID
- CDR0000352020
- Other IDs
- NCI-04-C-0079H, NCI-5643
- Status last verified
- Dec 2007
- First submitted
- 10 Feb 2004
- Last updated
- 28 Dec 2007
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pediatric Phase I Trial of BL22 for Refractory CD22-Positive Leukemias and Lymphomas
- ClinicalTrials.gov ID
- NCT00077493
- Acronym / sponsor ID
- CDR0000352020
- Keywords
- recurrent childhood acute lymphoblastic leukemia, Burkitt lymphoma, recurrent childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, childhood non-Hodgkin lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: protocol development and Amended protocol revision
- Enrolment
- 95 participants (estimated)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Collaborators
- Cambridge Antibody Technology
- Study start
- Jan 2004
- Primary completion
- Oct 2008 (estimated)
- Study completion
- Oct 2008 (estimated)
- First posted
- 12 Feb 2004 (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 locate tumor cells and kill them without harming normal cells. BL22 immunotoxin may be effective in treating relapsed or refractory acute lymphoblastic leukemia and non-Hodgkin's lymphoma.
PURPOSE: This phase I trial is studying the side effects and best dose of BL22 immunotoxin in treating young patients with relapsed or refractory acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES:
Primary
- Determine the toxic effects of BL22 immunotoxin in pediatric patients with relapsed or refractory CD22-positive acute lymphoblastic leukemia or non-Hodgkin's lymphoma.
- Determine the maximum tolerated dose of this drug in these patients.
- Determine the immunogenicity of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
Secondary
- Determine the in vitro cytotoxicity of this drug against lymphoblasts from patients with acute lymphoblastic leukemia.
- Determine the therapeutic efficacy of this drug in inducing remissions in these patients.
- Determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug.
OUTLINE: This is a non-randomized, dose-escalation study.
Patients receive BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses.
Cohorts of 3-6 patients receive escalating doses of 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. Once the MTD is determined, the cohort is expanded and a total of 12 patients are treated at that dose.
Patients are followed weekly for at least 1 month and then every 1-3 months thereafter.
PROJECTED ACCRUAL: A total of 95 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: BL22 immunotoxinBL22 immunotoxin |
| 2 | Active comparator | Procedure: antibody-drug conjugate therapyantibody therapy |
| 3 | Active comparator | Procedure: immunotoxin therapyimmunotoxin therapy |
| 4 | Active comparator | Procedure: monoclonal antibody therapymonoclonal antibody therapy |
Who may qualify
- Ages
- 6 months to 24 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 immunotoxinBL22 immunotoxin IV over 30 minutes on days 1, 3, and 5 OR on days 1, 3, 5, 7, 9, and 11. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) or unconfirmed CR (CRu) receive 2 additional courses beyond CR or CRu for a maximum of 6 courses. | Drug | 1 |
| antibody-drug conjugate therapyCD22 antibody, RFB4 on day 7 | Procedure or surgery | 2 |
| immunotoxin therapytested for immunogenicity to CAT-8015 before each cycle and at end of study. | Procedure or surgery | 3 |
| monoclonal antibody therapyadministered intravenously over 30 minutes. | Procedure or surgery | 4 |
Primary outcome
assessment of efficacy, safety, pharmacokinetics, immunogenicity.
Time frame: end of study
1 secondary outcome
Expansion of MTD
Time frame: end of study
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2007.
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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.
Alan S. Wayne, 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: paused, as of the sponsor's last update on 28 Dec 2007. 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?
Results are not available in the source record.
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.
What does the primary outcome measure?
assessment of efficacy, safety, pharmacokinetics, immunogenicity. (time frame: end of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Dec 2007.