Pyrimethamine to Treat Autoimmune Lymphoproliferative Syndrome
Status:
Completed
Trial end date:
2005-06-01
Target enrollment:
Participant gender:
Summary
This study will examine whether the drug pyrimethamine can shrink lymph nodes and spleen in
patients with autoimmune lymphoproliferative syndrome (ALPS). In this disease, lymphocytes
(white blood cells) do not die as they normally would. As a result, patients have enlarged
lymph glands, spleen, or liver, and other problems that may involve blood cell counts and
autoimmune disease (overactivity of the immune system). Pyrimethamine is an orally
administered antibiotic that has been used to treat or prevent malaria and toxoplasma, and
may be effective in shrinking lymph nodes and spleen.
Patients with ALPS who are between 2 and 70 years of age and have had lymph gland enlargement
for at least 1 year may be eligible for this study. Candidates will be screened with a
medical history and physical examination, blood tests, and possibly a bone marrow test.
Females of reproductive age will be screened with a urine pregnancy test. Women who are
capable of becoming pregnant must use an effective method of birth control during the entire
study period, because, taken during early months of pregnancy, pyrimethamine can cause birth
defects in the fetus. Women who are pregnant or nursing are excluded from the study.
Participants will undergo the following tests and procedures:
- CT scan: For this test, the patient lies still in the CT scanner while images are taken
of the neck, chest, and stomach area. A contrast dye is injected into a vein to brighten
the CT images. Very young children will be evaluated on a case by case basis to
determine whether a CT scan will be performed.
- Bone marrow biopsy: Participants undergo this test to rule out underlying bone marrow
disease if they have not had a bone marrow test done in the last six months prior to
enrolling in pyrimethamine study, as pyrimethamine can affect bone marrow function.
Under local anesthesia, a needle is inserted into the back part of the hipbone and a
small amount of marrow is removed. (Children are sedated for this test.)
- Leukapheresis: This is a procedure for collecting a small proportion of circulating
white blood cells while conserving the majority of blood cells. Specifically, blood is
drawn from a needle placed in an arm vein and is directed into a cell separator machine,
which separates the blood cells by spinning. A small proportion of circulating white
cells are removed, and the red cells, platelets, plasma and majority of white cells are
returned to the patient's blood circulation. Only patients who are 7 years of age or
older and weigh at least 55 pounds undergo this procedure. Other participants who choose
not to have apheresis will have about 3 tablespoons of blood drawn instead.
- Pyrimethamine administration: When the above tests are completed, participants begin
taking pyrimethamine. The dose is determined according to the individual's weight and is
gradually increased during the study period. Patients take the drug twice a week for a
total of 12 weeks.
- Blood tests: Blood samples are collected during weeks 2, 4, 6, 8, and 10 after beginning
treatment, and 2 weeks after the last dose of pyrimethamine. The purpose of these blood
tests is to check for possible drug-related side effects. Patients who develop a skin
rash, mouth sores or other side effects may have one or more doses of the treatment drug
withheld. When indicated, the patient will be directed to stop taking the study drug. If
needed, drug side effects will be treated with a vitamin supplement, folinic acid, taken
by mouth, 3 times weekly.
- Evaluations at the NIH Clinical Center will comprise of a pretreatment visit, one end of
treatment visit at the end of 12 weeks and an optional post-treatment visit 3months
after stopping pyrimethamine therapy.
Patients who respond well to treatment may be asked to return to NIH for additional visits at
3, 6, and 12 months after the treatment has ended for repeat evaluations. If their lymph
glands or spleen become much larger after stopping pyrimethamine, they will be offered
treatment for another 12 weeks. If they respond to the second course of treatment, they will
return to NIH again after 3, 6, and 12 months. If the symptoms return again, patients will be
asked to resume treatment for an additional 6 months or more. They will have blood drawn
periodically by their private physician and will return to NIH for evaluation every 12 weeks.
Phase:
Phase 1
Details
Lead Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)