National Cancer Institute - U.S. National Institutes of Health - www.cancer.gov
National Cancer Institute - U.S. National Institutes of Health - www.cancer.gov

Trial FAQs

Phase II Study of LMB-2 Immunotoxin in Patients With CD25-Positive Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia

Protocol # 04-C-0121

Why is this trial important?

Patients with chronic lymphocytic leukemia have many options for therapy but many have malignant cells that do not respond well to any standard therapy. These cells often display the marker CD25, which makes them potential targets for the recombinant immunotoxin LMB-2.

Who is eligible for this trial? (PDQ)

  • Histologically confirmed chronic lymphocytic leukemia, including prolymphocytic leukemia
  • CD25-positive disease
    • At least 50% of peripheral malignant lymphocytes are CD25+ by fluorescence-activated cell sorting (FACS) with anti-CD25 antibody* NOTE: *Positive expression in FACS assay is defined as > 2 times the mean fluorescence intensity of the control antibody by FACS
  • Intermediate- or high-risk disease, meeting the following criteria:
    • Lymphocytosis (leukemic cells > 5,000/mm) AND has at least one of the following:
      • Lymphadenopathy
      • Splenomegaly
      • Hepatomegaly
      • Anemia (hemoglobin < 11g/dL)
      • Thrombocytopenia (platelet count < 100,000/mm3)
  • Progressive disease after prior standard therapy containing either a purine analog or an alkylating agent
  • No serum neutralizing LMB-2 immunotoxin in tissue culture (due to either anti-toxin or anti-mouse-immunoglobulin G antibodies)
  • No serum neutralizing > 75% of the activity of 1 μg/mL of LMB-2 immunotoxin
  • 18 and over
  • ECOG 0-2
  • ALT and AST ≤ 2.5 times upper limit of normal (ULN), albumin ≥ 3.0 g/dL, bilirubin ≤ 2.2 mg/dL (< 5 mg/dL in patients with Gilbert's syndrome), hepatitis B surface antigen negative unless patient is receiving treatment with lamivudine, no hepatitis C, no chronic liver disease
  • Creatinine ≤ 1.4 mg/dL OR Creatinine clearance ≥ 50 mL/min
  • LVEF ≥ lower limit of normal, no symptomatic congestive heart failure, no unstable angina pectoris, no cardiac arrhythmia
  • DLCO ≥ 55% of normal, FEV_1 ≥ 60% of normal
  • HIV negative, no ongoing or active infection
  • No other concurrent uncontrolled illness

What types of drugs or therapies are being used?

Recombinant immunotoxin LMB-2, a protein composed of a binding antibody part, and a toxin. After binding to and being internalized by target cells, the toxin kills the cell with extreme potency. LMB-2 therefore kills leukemia cells directly without needing help from the immune system, which is often damaged due to leukemia and prior treatment.

What is the treatment plan? (PDQ)

  • 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 1μg/mL of LMB-2 immunotoxin), or unacceptable toxicity
  • Patients who achieve a complete response receive up to 2 additional courses of LMB-2 immunotoxin
  • Patients who relapse after achieving a complete or partial response for more than 2 months are eligible for retreatment as described above
  • Patients are followed every 3-12 months until disease progression

What is the frequency and duration of the visits?

Blood samples are sent ahead of time and tested free of charge at NIH to determine eligibility. During the first visit, patients typically spend 3 days taking baseline tests. When treatment begins, a cycle includes treatment by 30-minute infusion every other day for 3 doses, and patients usually return home a week after beginning. Patients who have not made antibodies against LMB-2 and whose disease has not worsened on treatment may be eligible for additional cycles at approximate monthly intervals. LMB-2 may be given as an inpatient or outpatient.

What are the costs?

There is no charge for medical care received at the National Institutes of Health (NIH) Clinical Center. Patients will be responsible for travel costs for their initial screening visits. In most cases, once patients are enrolled in a trial, the National Cancer Institute (NCI) will pay the transportation costs for all subsequent trial-related visits for patients who do not live in the local area. In addition, these patients will receive a small per diem to help offset the costs of meals and lodging if they are being treated as outpatients.

It will be important to maintain your current insurance plan to cover all medical care that is provided away from the NIH Clinical Center.

No U.S. citizen or permanent U.S. resident residing in the U.S. who otherwise meets the eligibility requirements will be denied enrollment in clinical research protocols because of their inability to pay the costs of travel and subsistence.

Who is the Principal Investigator?

Dr. Robert J. Kreitman received his M.D. from Ohio State University in 1985 and obtained his internal medicine residency training at Duke University from 1985 to 1988. He received his medical oncology fellowship training at the NIH from 1988 to 1991, has been working in the immunotoxin field since 1989, and has been directing clinical trials with immunotoxins since 1996. He won Federal Technology Transfer awards in 1994 and 1999-2005. He has won several awards from the U.S. Public Health Service, including the Commendation Medal 1999 and the Outstanding Service Medal in 2002.

Where is this trial taking place?

Warren Grant Magnuson Clinical Center
National Institutes of Health
NCI Laboratory of Molecular Biology
10 Center Drive
Bethesda, Maryland 20892

Who are the contacts for this trial?

Robert J. Kreitman, M.D.
Principal Investigator
Phone: 301-496-6947
kreitmar@mail.nih.gov

Referrals:

Linda Ellison, R.N.
Research Nurse
Phone: 301-496-9458
Fax: 240-220-7677
ellisonl@mail.nih.gov

Rita Mincemoyer, R.N.
Research Nurse
Phone: 301-594-1778
Fax: 240-220-7677
mincemor@mail.nih.gov

Elizabeth Maestri, R.N.
Research Nurse
Phone: 301-402-5633
Fax: 240-220-7677
maestrie@mail.nih.gov

Where can additional information be found?

Back to Top
Health and Human Services National Institutes of Health National Cancer Institute USA.gov National Cancer Institute Clinical Trials at NIH - Be part of the cure