Pyrimethamine to Treat Autoimmune Lymphoproliferative Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00065390
• Date of registration: 21/07/2003
• Prospective Registration: No
• Primary sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Public title: Pyrimethamine to Treat Autoimmune Lymphoproliferative Syndrome
• Scientific title: Pilot (Phase I-II) Study of Pyrimethamine (Daraprim) for the Treatment of the Autoimmune Lymphoproliferative Syndrome (ALPS)
• Date of first enrolment: July 2003
• Target sample size: 8
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00065390
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Key inclusion & exclusion criteria

INCLUSION CRITERIA:

All subjects must fulfill the published 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). This must include clinically documented
lymphadenopathy involving more than two nodes in more than one regional group of nodes
measuring greater than 1 cm in size and/or a palpable spleen.

Age greater than 2 years and less than 70 years.

Must have a personal primary care physician.

Women of reproductive age and potential must have a negative pregnancy test at study entry
and commit to using an acceptable method of barrier or hormonal contraception (e.g.
condoms, diaphragms, oral contraceptives and long acting progestin agents) if sexually
active during the study and for 3 months after the last dose of pyrimethamine.

Must be willing to sign a consent form.

EXCLUSION CRITERIA:

Patient will be excluded if any of the following is present:

Weight of less than 10 kilograms (22 lbs).

Patients receiving and requiring anti-folate drugs such as sulfonamides, trimethoprim,
pyrimethamine and methotrexate for any other purpose. They should be off these
medications, including Bactrim, for at least 7 days prior to enrolling in this protocol.

Megaloblastic anemia, folate deficiency or a mean corpuscular volume greater than 125 in
last three months with evidence of megaloblastic changes in the bone marrow.

A hemoglobin concentration of less than 8 gm/dl, a platelet count of less than 50 K/mm(3),
or an absolute neutrophil count of less than 500/mm(3), at study entry or during the study
period.

Liver disease determined by an ALT, AST or bilirubin 3 times above the upper limit of
normal.

Renal dysfunction determined by a calculated urine 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 or
using the Schwartz formula or Levy formula based on serum creatinine.

Patients on immunosuppression (eg: corticosteroid, azathioprine, cyclosphosphamide, etc)
are eligible if the dose of the immunosuppressive drug has been stable for at least 3
months prior to enrollment and their hematologic parameters meet the criteria outlined in
item 4 (above).

Pregnancy. Women of reproductive age and potential must have a negative pregnancy test at
study entry and commit to using an acceptable method of barrier or hormonal contraception
(e.g. condoms, diaphragms, oral contraceptives and long acting progestin agents) if
sexually active during the study and for 3 months after the last dose of pyrimethamine.

Lactating mothers who are breast feeding their babies will not be eligible.

ALPS patients who have been treated with bone marrow toxic chemotherapy regimens for
Hodgkins and Non-Hodgkins lymphoma or other malignancies are not eligible for this pilot
study.

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.



Age minimum: N/A
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Lymphoproliferative Disorder

Autoimmune Disease

Lymphatic Disease

Intervention(s)

Drug: Pyrimethamine

Secondary ID(s)

030248

03-I-0248

Source(s) of Monetary Support

Please refer to primary and secondary sponsors