Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00013689
Other study ID # 010132
Secondary ID 01-I-0132
Status Completed
Phase Phase 1
First received March 28, 2001
Last updated March 3, 2008
Start date March 2001
Est. completion date March 2003

Study information

Verified date March 2003
Source National Institutes of Health Clinical Center (CC)
Contact n/a
Is FDA regulated No
Health authority United States: Federal Government
Study type Interventional

Clinical Trial Summary

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.


Description:

The Autoimmune Lymphoproliferative Syndrome is an inherited disease associated with a defect of lymphocyte apoptosis, lymphoproliferation and autoimmunity. Although, there are treatments for many of its autoimmune complications, there currently is no safe and effective therapy for this syndrome itself. Recently investigators in Europe serendipitously found that a child with ALPS type I had significant clinical improvement while on pyrimethamine/sulfadoxine (Fansidar) for Pneumocystis carinii prophylaxis.

Based on this finding, we propose to conduct a pilot study to obtain information on safety and initial data on efficacy of the drug combination Fansidar for the treatment of ALPS. Six to 8 individuals, with ALPS who report no allergy to sulfa drugs will be treated for up to 3 months with weekly Fansidar at escalating doses adjusted by weight. The effect of Fansidar treatment on lymph node and/or spleen size will be assessed by CT scanning. The effect of treatment on other laboratory features of ALPS will also be assessed. Evaluating the effects of Fansidar on these clinical and laboratory parameters will allow us to determine if this drug demonstrates sufficient activity to warrant further study in a larger randomized controlled trial.


Recruitment information / eligibility

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.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Fansidar (pyrimethamine and sulfadoxine)


Locations

Country Name City State
United States National Institute of Allergy and Infectious Diseases (NIAID) Bethesda Maryland

Sponsors (1)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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

See also
  Status Clinical Trial Phase
Recruiting NCT04883437 - Acalabrutinib and Obinutuzumab for the Treatment of Previously Untreated Follicular Lymphoma or Other Indolent Non-Hodgkin Lymphomas Phase 2
Recruiting NCT01137825 - Registry of Older Patients With Cancer
Suspended NCT00935090 - 3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer N/A
Active, not recruiting NCT00092222 - Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity Phase 2
Completed NCT00719563 - American Ginseng in Treating Patients With Fatigue Caused by Cancer Phase 3
Completed NCT00956475 - Quality of Life in Younger Leukemia and Lymphoma Survivors Phase 1
Terminated NCT00899951 - Studying Fentanyl in Patients With Cancer N/A
Completed NCT00646139 - KX2-391 in Treating Patients With Advanced Solid Tumors or Lymphoma That Did Not Respond to Treatment Phase 1
Active, not recruiting NCT00324597 - AMG 706 and Gemcitabine in Treating Patients With Advanced Solid Tumors or Lymphoma Phase 1
Withdrawn NCT00621036 - Vaccine Therapy and GM-CSF in Treating Patients With CNS Lymphoma Phase 2
Recruiting NCT02402244 - Project: Every Child for Younger Patients With Cancer
Terminated NCT00952185 - Influenza Vaccine in Preventing Flu in Patients Who Have Undergone Stem Cell Transplant and in Healthy Volunteers N/A
Active, not recruiting NCT00001379 - Treatment and Natural History Study of Lymphomatoid Granulomatosis Phase 2
Completed NCT01000753 - Collecting and Storing Tissue Samples From Patients With Rare or Cutaneous Non-Hodgkin Lymphoma
Completed NCT01273090 - Imetelstat Sodium in Treating Young Patients With Refractory or Recurrent Solid Tumors or Lymphoma Phase 1
Completed NCT00416624 - Epoetin Alfa or Darbepoetin Alfa in Treating Patients With Anemia Caused by Chemotherapy Phase 2
Withdrawn NCT00387530 - Phenylbutyrate and Valganciclovir in Treating Patients With Relapsed or Refractory Epstein-Barr Virus-Positive Cancer Phase 2
Completed NCT00666211 - Opioid Titration Order Sheet or Standard Care in Treating Patients With Cancer Pain Phase 3
Terminated NCT00087009 - Beta-Glucan and Rituximab in Treating Young Patients With Relapsed or Progressive Lymphoma or Leukemia, or Lymphoproliferative Disorder Related to Donor Stem Cell Transplantation Phase 1
Terminated NCT00726830 - Methadone, Morphine, or Oxycodone in Treating Pain in Patients With Cancer N/A