Lymphoproliferative Disorder Clinical Trial
Official title:
Pilot Study of Pyrimethamine and Sulfadoxine (Fansidar) for the Treatment of Individuals With the Autoimmune Lymphoproliferative Syndrome (ALPS)
This study will evaluate the safety and effectiveness of an antibiotic called Fansidar on
autoimmune lymphoproliferative syndrome (ALPS). Patients with ALPS have enlarged lymph
glands, spleen and/or liver, abnormal blood cell counts and overactive immune function.
Current treatments are aimed at suppressing the immune system and improving symptoms, such
as anemia (low red blood cell count) and low white blood cell and platelet counts. These
treatments, however, are only partially effective and may have complications. Fansidar is a
combination of two drugs, sulfadoxine and pyrimethamine, that is used to treat or prevent
parasitic infections such as malaria. Recently a child with ALPS who was treated with
Fansidar for a different illness had a marked shrinkage of the lymph organs. This study will
examine whether Fansidar can shrink the lymph glands or spleen in patients with ALPS.
Patients with ALPS between the ages of 4 and 70 years who have had lymph gland enlargement
for at least 1 year and are not allergic to sulfa drugs may be eligible for this study.
Candidates will be screened with a medical history and physical examination and blood tests.
Females of reproductive age will have a urine pregnancy test.
Participants will be evaluated at the NIH Clinical Center in Bethesda, MD, with blood tests
and a computed tomography (CT) scan of the lymph nodes. For the CT scan, the patient lies on
a table during an X-ray scan of the neck, part of the chest, and, if the spleen has not been
removed, the stomach area.
When these baseline tests are completed, patients will be given Fansidar pills to take once
a week for 12 weeks. The dosage will be increased after 2 weeks and again after 4 weeks. At
2, 4, 6, 8 and 10 weeks after starting the treatment and 2 weeks after the last dose,
patients will have blood drawn to check for possible side effects of therapy. Women will
have a repeat urine pregnancy test at week 6 of treatment.
Within a week before completing treatment or after completing treatment, patients will
return to NIH for a history, physical examination, blood tests and CT scan. Patients who
responded well to treatment will be offered to return to NIH again 3, 6 and 12 months later
to repeat the evaluations. If ALPS symptoms recur during this time, patients will be offered
another 12-week course of Fansidar and the procedure, including the 3, 6 and 12-month
evaluations will be repeated again. If symptoms recur again, patients will be asked to
resume Fansidar for 6 months or longer, with doses adjusted as needed. During this time,
patients will be seen at NIH every 12 weeks for evaluation and blood will be drawn by the
patient's private physician every 6 weeks or 2 and 4 weeks after the dose is increased to
check for side effects.
Status | Completed |
Enrollment | 8 |
Est. completion date | March 2003 |
Est. primary completion date | |
Accepts healthy volunteers | No |
Gender | Both |
Age group | N/A and older |
Eligibility |
INCLUSION CRITERIA All subjects must fulfill the current criteria for the diagnosis of ALPS (documented nonmalignant lymphadenopathy and/or splenomegaly of at least 1 year duration; greater than or equal to 1% TCR alpha/beta(+) CD4 (-) CD8(-) T cells in the peripheral blood and defective apoptosis by in vitro assay). Subjects must be between 4 to 70 years of age. Subjects must have a primary care physician. EXCLUSION CRITERIA Weigh less than 18 kgs (40 lbs.) will be excluded. Have a known hypersensitivity reaction to pyrimethamine, sulfonamides, sulfonylureas, furosemide or other sulfa-like drugs will be excluded. If you are receiving and requiring anti-folate drugs such as sulfonamides, trimethoprim, pyrimethamine and methotrexate will be excluded. Patients who are G-6-PD deficient will be excluded. Have a history of megaloblastic anemia, folate deficiency or a mean corpuscular volume greater than 101 CU MICR will be excluded. Have a usual Hb concentration of less than 9 gm/dl, a platelet count of less than 75 K/mm(3), or an absolute neutrophil count of less than 1000/mm(3) will be excluded. Liver disease determined by an ALT, AST or bilirubin 3 times above the upper limit of normal, and/or a serum albumin of less than 3 gm/dL will be excluded. Renal dysfunction determined by a calculated creatinine clearance of less than or equal to 70 ml/min/1.73 m(2) in children and less than or equal to 60 ml/min in adults will be excluded. Patients on immunosuppression (eg: corticosteroid, azathioprine, cyclophosphamide, etc.) are not eligible if the dose of the immunosuppressive drug has not been stable for at least 6 months prior to enrollment will be excluded. Pregnant women will be excluded. Women of reproductive age must have a negative pregnancy test and commit to use an acceptable method of contraception. Unwilling or unable to comply with the need to have periodic blood tests to monitor possible side effects of treatment, or other major requirements of this study. |
Endpoint Classification: Safety Study, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | National Institute of Allergy and Infectious Diseases (NIAID) | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Institute of Allergy and Infectious Diseases (NIAID) |
United States,
Avila NA, Dwyer AJ, Dale JK, Lopatin UA, Sneller MC, Jaffe ES, Puck JM, Straus SE. Autoimmune lymphoproliferative syndrome: a syndrome associated with inherited genetic defects that impair lymphocytic apoptosis--CT and US features. Radiology. 1999 Jul;212(1):257-63. — View Citation
Straus SE, Sneller M, Lenardo MJ, Puck JM, Strober W. An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome. Ann Intern Med. 1999 Apr 6;130(7):591-601. Review. — View Citation
van der Werff ten Bosch JE, Demanet C, Balduck N, Bakkus MH, De Raeve H, Desprechins B, Otten J, Thielemans K. The use of the anti-malaria drug Fansidar (pyrimethamine and sulphadoxine) in the treatment of a patient with autoimmune lymphoproliferative syndrome and Fas deficiency. Br J Haematol. 1998 Jul;102(2):578-81. — View Citation
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