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Pediatric Phase I Trial of LMB-2 for Refractory CD25-Positive Leukemias and Lymphomas

Phase 1
21 Years
Not Enrolling
Leukemia, Lymphoma

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Trial Information

Pediatric Phase I Trial of LMB-2 for Refractory CD25-Positive Leukemias and Lymphomas



- 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

Inclusion Criteria


- 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

- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Alan S. Wayne, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Food and Drug Administration

Study ID:




Start Date:

April 2004

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • 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
  • Leukemia
  • Lymphoma



Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Winship Cancer Institute of Emory University Atlanta, Georgia  30322
Doernbecher Children's Hospital at Oregon Health & Science University Portland, Oregon  97239-3098
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182