LMB-2 Immunotoxin in Treating Young Patients With Relapsed or Refractory Leukemia or Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00085150
Recruitment Status : Completed
First Posted : June 11, 2004
Last Update Posted : April 30, 2015
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Biological: LMB-2 immunotoxin Phase 1

Detailed Description:



  • 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.


  • 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 : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Primary Purpose: Treatment
Official Title: Pediatric Phase I Trial of LMB-2 for Refractory CD25-Positive Leukemias and Lymphomas
Study Start Date : April 2004

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 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


  • 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)


  • Bilirubin ≤ 2.0 mg/dL
  • AST and ALT ≤ 5 times upper limit of normal
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative


  • 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


  • Ejection fraction ≥ 45% by MUGA OR
  • Shortening fraction ≥ 28% by echocardiogram


  • Oxygen saturation ≥ 90%


  • 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)


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)


  • 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


  • At least 3 weeks since prior radiotherapy unless < 10% of marrow is irradiated and measurable disease exists outside the radiation port


  • Not specified


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00085150

United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
United States, Oregon
Doernbecher Children's Hospital at Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Alan S. Wayne, MD National Cancer Institute (NCI) Identifier: NCT00085150     History of Changes
Obsolete Identifiers: NCT00082004
Other Study ID Numbers: CDR0000367333
First Posted: June 11, 2004    Key Record Dates
Last Update Posted: April 30, 2015
Last Verified: February 2007

Keywords provided by National Cancer Institute (NCI):
recurrent adult T-cell leukemia/lymphoma
recurrent childhood acute lymphoblastic leukemia
childhood Burkitt lymphoma
recurrent childhood acute myeloid leukemia
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
relapsing chronic myelogenous leukemia
acute undifferentiated leukemia

Additional relevant MeSH terms:
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs