- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00085150
LMB-2 Immunotoxin in Treating Young Patients With Relapsed or Refractory Leukemia or Lymphoma
Pediatric Phase I Trial of LMB-2 for Refractory CD25-Positive Leukemias and Lymphomas
RATIONALE: LMB-2 immunotoxin can locate cancer cells and kill them without harming normal cells.
PURPOSE: This phase I trial is studying the side effects and best dose of LMB-2 immunotoxin in treating young patients with relapsed or refractory leukemia or lymphoma.
Study Overview
Status
Intervention / Treatment
Detailed Description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of LMB-2 immunotoxin in pediatric patients with CD-25 positive relapsed or refractory leukemia or lymphoma.
- Determine the toxic effects of this drug in these patients.
- Determine the pharmacokinetics of this drug, including the terminal elimination serum half-life, area under the curve, volume of distribution, and relationship to disease burden, in these patients.
Secondary
- Evaluate the immonogenicity of this drug in these patients.
- Determine response in patients treated with this drug.
- Determine changes in lymphocyte subsets, immunoglobulin levels, serum cytokines, and soluble cytokine receptor levels in patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression, neutralizing antibodies (i.e., > 75% of the activity of 1 µg/mL of LMB-2 immunotoxin), or unacceptable toxicity. Patients achieving complete remission (CR) receive 2 additional courses beyond CR. Patients with acute lymphoblastic leukemia also receive cytarabine and hydrocortisone intrathecally once monthly concurrent with restaging lumbar punctures.
Cohorts of 3-6 patients receive escalating doses of LMB-2 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, a total of 12 patients are treated at that dose level.
Patients are followed weekly for 1 month and then monthly thereafter.
PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 2-4 years.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Georgia
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Atlanta, Georgia, United States, 30322
- Winship Cancer Institute of Emory University
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Maryland
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Baltimore, Maryland, United States, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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Bethesda, Maryland, United States, 20892-1182
- Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
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Oregon
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Portland, Oregon, United States, 97239-3098
- Doernbecher Children's Hospital at Oregon Health & Science University
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Tennessee
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Memphis, Tennessee, United States, 38105
- St. Jude Children's Research Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following:
Non-Hodgkin's lymphoma, including the following subtypes:
- Lymphoblastic lymphoma
- Burkitt's lymphoma
- Large cell lymphoma
- Adult T-cell leukemia/lymphoma
- Cutaneous T-cell lymphoma
- Peripheral T-cell lymphoma
- Hodgkin's disease
- Acute myeloid leukemia
- Chronic myelogenous leukemia
Acute lymphoblastic leukemia (ALL)
- More than 5% blasts in the bone marrow (i.e., M2 marrow classification)
Acute hybrid leukemia, including the following subtypes:
- Mixed lineage leukemia
- Biphenotypic leukemia
- Undifferentiated leukemia
CD25-positive (CD25+) disease, meeting 1 of the following criteria:
- More than 15% of malignant cells are CD25+ by immunohistochemistry with anti-CD25 antibody
- More than 30% of malignant cells from a site are CD25+ by fluorescence-activated cell sorting analysis
- Measurable or evaluable disease
- Relapsed or refractory disease after at least 1 standard chemotherapy regimen AND 1 salvage regimen
- No available alternative curative therapies
- Ineligible for or refused hematopoietic stem cell transplantation OR disease activity that prohibits the required time to identify a suitable stem cell donor
No CNS leukemia or lymphoma, as evidenced by any of the following criteria:
- Cerebrospinal fluid (CSF) WBC > 5/µl AND confirmation of CSF blasts
- Cranial neuropathies secondary to underlying malignancy
CNS lymphoma detected by radiological imaging
- Prior CNS involvement with no current evidence of CNS malignancy allowed
- No isolated testicular ALL
PATIENT CHARACTERISTICS:
Age
- 6 months to 21 years
Performance status
- ECOG 0-3 (≥ 12 years of age)
- Lansky 40-100% (< 12 years of age)
Life expectancy
- Not specified
Hematopoietic
- Pancytopenia due to disease allowed
For patients without bone marrow involvement:
- Absolute neutrophil count > 1,000/mm^3
- Platelet count > 50,000/mm^3 (transfusion independent)
Hepatic
- Bilirubin ≤ 2.0 mg/dL
- AST and ALT ≤ 5 times upper limit of normal
- Hepatitis B surface antigen negative
- Hepatitis C antibody negative
Renal
- Creatinine clearance ≥ 60 mL/min OR
Creatinine, meeting the following age-related criteria:
- ≤ 0.8 mg/dL (≤ 5 years of age)
- ≤ 1.0 mg/dL (6 to 10 years of age)
- ≤ 1.2 mg/dL (11 to 15 years of age)
- ≤ 1.5 mg/dL (> 15 years of age)
- Calcium 2.0-2.9 mmol/L
Cardiovascular
- Ejection fraction ≥ 45% by MUGA OR
- Shortening fraction ≥ 28% by echocardiogram
Pulmonary
- Oxygen saturation ≥ 90%
Other
- Sodium 130-150 mmol/L
- Potassium 3.0-5.5 mmol/L
- Magnesium 0.5-1.23 mmol/L
- HIV negative
- 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 conditions that would preclude study compliance
- No serum that neutralizes > 75% of the activity of 1 μg/mL of LMB-2 immunotoxin in tissue culture (due to either anti-toxin or anti-mouse immunoglobulin G antibodies)
- No active graft-vs-host disease (i.e., off immunosuppression)
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Prior autologous bone marrow transplantation (BMT) allowed
- At least 100 days since prior allogeneic BMT
- At least 1 week since prior colony-stimulating factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], or epoetin alfa)
Chemotherapy
- At least 2 weeks since prior chemotherapy (4 weeks for nitrosoureas) except intrathecal chemotherapy
- No other concurrent chemotherapy
Endocrine therapy
Concurrent corticosteroids allowed provided the dose has been stable for the past week and does not increase during study treatment
- Tapering or discontinuation of steroids allowed
Radiotherapy
- At least 3 weeks since prior radiotherapy unless < 10% of marrow is irradiated and measurable disease exists outside the radiation port
Surgery
- Not specified
Other
- Recovered from all prior therapy
- At least 30 days since prior investigational agents
- Concurrent oral supplementation to maintain normal electrolyte levels allowed
- No concurrent anticoagulation therapy for disease-related conditions
- No other concurrent investigational agents
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Alan S. Wayne, MD, National Cancer Institute (NCI)
Study record dates
Study Major Dates
Study Start
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- childhood Burkitt lymphoma
- recurrent childhood large cell lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- relapsing chronic myelogenous leukemia
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- recurrent adult T-cell leukemia/lymphoma
- recurrent mycosis fungoides/Sezary syndrome
- recurrent childhood acute lymphoblastic leukemia
- recurrent childhood acute myeloid leukemia
- recurrent childhood lymphoblastic lymphoma
- acute undifferentiated leukemia
Additional Relevant MeSH Terms
Other Study ID Numbers
- CDR0000367333
- NCI-04-C-0168
- NCI-5903
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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