Autoimmune DiseasePhase 1NCT00013689
Pyrimethamine and Sulfadoxine for Treatment of Autoimmune Lymphoproliferative Syndrome
A Phase 1 study testing Fansidar (pyrimethamine and sulfadoxine) in people with Autoimmune Disease and Lymphoproliferative Disorder, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Autoimmune Disease, Lymphoproliferative Disorder
- What is being tested?
- Fansidar (pyrimethamine and sulfadoxine)
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2001to Mar 2003
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Allergy and Infectious Diseases (NIAID)
Bethesda, Maryland, 20892
About this study
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.
Read more
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.
Read the detailed 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.
- Conditions
- Autoimmune Disease, Lymphoproliferative Disorder
- Being tested
- Fansidar (pyrimethamine and sulfadoxine)
- Keywords
- Lymphadenopathy, Splenomegaly, Children, Tomography, Autoimmune Lymphoproliferative Syndrome (ALPS)
- Medical subject headings
- Autoimmune Diseases, Lymphoproliferative Disorders, Lymphadenopathy, Splenomegaly, Autoimmune Lymphoproliferative Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fansidar (pyrimethamine and sulfadoxine)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2001 (estimated)
- Study startMar 2001
- Study completionMar 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Autoimmune DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 8 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00013689
- Sponsor's protocol ID
- 010132
- Other IDs
- 01-I-0132
- Status last verified
- Mar 2003
- First submitted
- 28 Mar 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
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. doi: 10.1046/j.1365-2141.1998.00791.x.
PubMed 9695976Straus 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. doi: 10.7326/0003-4819-130-7-199904060-00020.
PubMed 10189330Avila 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. doi: 10.1148/radiology.212.1.r99jl40257.
PubMed 10405750
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Pyrimethamine and Sulfadoxine (Fansidar) for the Treatment of Individuals With the Autoimmune Lymphoproliferative Syndrome (ALPS)
- ClinicalTrials.gov ID
- NCT00013689
- Acronym / sponsor ID
- 010132
- Conditions
- Autoimmune Disease, Lymphoproliferative Disorder
- Keywords
- Lymphadenopathy, Splenomegaly, Children, Tomography, Autoimmune Lymphoproliferative Syndrome (ALPS)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Mar 2001
- Study completion
- Mar 2003
- First posted
- 29 Mar 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fansidar (pyrimethamine and sulfadoxine) | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 9695976van 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. doi: 10.1046/j.1365-2141.1998.00791.x.
- Background: PubMed 10189330Straus 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. doi: 10.7326/0003-4819-130-7-199904060-00020.
- Background: PubMed 10405750Avila 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. doi: 10.1148/radiology.212.1.r99jl40257.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fansidar (pyrimethamine and sulfadoxine) in people with Autoimmune Disease and Lymphoproliferative Disorder, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00013689, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.