Autoimmune DiseasePhase 1NCT00001630
Treatment of Autoimmune Thrombocytopenia (AITP)
A Phase 1 study testing Isolex 300i in people with Autoimmune Disease and Autoimmune Hemolytic Anemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Platelets are particles found along with red and white blood cells in the blood that play a role in the process of blood clotting. Disorders affecting the platelets can lower the amount of platelets in the blood and put patients at risk of bleeding. The condition of low platelets is referred to as thrombocytopenia. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Autoimmune Disease, Autoimmune Hemolytic Anemia, Thrombocytopenia
- What is being tested?
- Isolex 300i
- Type of treatment
- Medical device
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Jul 1997to 11 Jun 2009
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, ages 18-65 years old.
- Refractory severe chronic autoimmune thrombocytopenia, with or without autoimmune hemolytic anemia (Evan's syndrome), with all the following:
- Platelet count frequently below 20,000/mm(3) despite active
- treatment for a period of greater than 6 months.
- Normal or increased megakaryocytes on bone marrow
- aspirate/bx.
Show all 17Show fewer
- No plausible alternative etiology such as drug-mediated
- thrombocytopenia, marrow failure syndrome or thrombocytopenia
- related to viral or bacterial infection.
- Failure of treatment with:
- conventional-dose steroids (e.g., prednisone or dosage of 40
- mg/day or equivalent, followed by dosage taper) for at least 3
- months.
- intravenous immunoglobulin.
- splenectomy.
- Episodic bleeding requiring transfusions or ecchymoses interfering
- with ordinary daily activities.
Who cannot join
- ECOG performance status greater than 1.
- Cardiopulmonary disease including:
- History of coronary artery disease, angina pectoris or congestive heart failure.
- LV ejection fraction less than 40 percent by 2D echocardiogram.
- Renal disease, serum creatinine greater than 2.5 mg/dL or creatinine clearance less than 30 mL/min.
- Significant hepatic dysfunction, bilirubin greater than 2 mg/dL or transaminases greater than 2 times UNL.
Show all 13Show fewer
- Uncorrected coagulopathy.
- Bone marrow aplasia (cellularity less than 10 percent), single or multilineage hematopoietic failure, myelodysplastic syndrome, or extensive marrow fibrosis.
- History or active diagnosis of malignancy (except treated non-melanoma skin cancer or cevical carcinoma in situ).
- HIV positive.
- Pregnancy or lactation, unwillingness to practice adequate birth control in the peritransplant period.
- Psychiatric illness or mental incapacity to understand and give informed consent.
- Other medical illness or condition which, in the opinion of the Investigators, may contraindicate participation in this study due to patients' risk or compromise of study integrity.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: High-Dose Cyclophosphamide With CD34+ Selected Autologous Hematopoietic Cell Support for Treatment of Refractory Chronic Autoimmune Thrombocytopenia
Platelets are particles found along with red and white blood cells in the blood that play a role in the process of blood clotting. Disorders affecting the platelets can lower the amount of platelets in the blood and put patients at risk of bleeding. The condition of low platelets is referred to as thrombocytopenia.
Thrombocytopenia can be associated with a variety of diseases including cancer, leukemia, tuberculosis, or as a result of an autoimmune reaction. Autoimmune reactions are disorders in which the normal immune system begins attacking itself. Autoimmune thrombocytopenia (AITP) is a disorder of low blood platelet counts in which platelets are destroyed by antibodies produced by the immune system.
Read more
Unfortunately, many patients with AITP do not respond to standard treatments for thrombocytopenia. Cyclophosphamide is a drug that works to suppress the activity of the immune system. Researchers believe that combining this drug with transplanted rescued blood stem cells may provide effective treatment for AITP.
The purpose of this study is to explore the affordability and safety of this therapy for the treatment of AITP. The effectiveness of the therapy will be measured by the number of patients whose platelet levels rise greater than 100,000/m3.
If this treatment approach appears affordable, this study will form the basis for a larger study to compare alternate treatment approaches.
Read the detailed description
Autoimmune Thrombocytopenia (AITP) is a disorder of low blood platelet counts in which platelet destruction is caused by antiplatelet autoantibodies. A large proportion of patients with chronic AITP are refractory to standard therapies including corticosteroids, immune globulin and splenectomy. Cyclophosphamide is a cytotoxic immunosuppressive agent which may induce durable remissions of refractory autoimmune diseases. High-dose cyclophosphamide with peripheral blood stem cell (PBPC) rescue has been proposed as a potential definitive therapy for AITP; however, the infusion of autoreactive lymphocytes could result in relapse. The use of PBPC depleted of T-lymphocytes could circumvent this limitation.
The purpose of this phase I/II study is to explore the feasibility and safety of this approach, and to seek preliminary evidence of effectiveness, of using high-dose cyclophosphamide (50 mg/kg/day x 4) followed by infusion of autologous PBPC enriched for CD34+ cells (concomitantly depleted of CD3+ cells) for the treatment of patients with refractory AITP. Safety/feasibility parameters to be examined will include the ability to mobilize, harvest and purify sufficient PBPC to yield greater than 2 x 10(6) CD34+ cells/kg; symptomatic acceptability and hematologic toxicities of the mobilization regimen (filgrastim 10 micrograms/kg/day IV); tolerability of the leukapheresis procedure, including the central line placement and maintenance; depth and duration of blood cell nadirs following chemotherapy; peritransplant bleeding episodes and transfusion requirements; episodes of febrile neutropenia, culture-proven infections and antibiotic usage. Effectiveness will be gauged by the rapidity and number of patients to achieve complete remission (platelet count greater than 100,000/mm(3) and partial remission (platelet count greater than 50,000/mm(3) or doubling of the platelet count with resolution of bleeding episodes). Ancillary evidence of therapeutic effect will be sought by examining changes in titers of platelet surface glycoprotein antibodies. In addition, alterations in T-lymphocyte subsets will be examined by flow cytometry. If this treatment approach appears feasible, this study will form the basis for a larger trial to compare alternate treatment approaches.
- Being tested
- Isolex 300i
- Keywords
- Immunosuppression, Thrombocytopenia, Autoimmune Disease, Evan's Syndrome, Autoimmune Hemolytic Anemia, Episodic Bleeding
- Medical subject headings
- Autoimmune Diseases, Anemia, Hemolytic, Autoimmune, Thrombocytopenia, Evans Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isolex 300iDevice
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start21 Jul 1997
- Study completion11 Jun 2009
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 Heart, Lung, and Blood Institute (NHLBI)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
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001630
- Sponsor's protocol ID
- 970154
- Other IDs
- 97-H-0154
- Status last verified
- 21 Mar 2011
- First submitted
- 3 Nov 1999
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Semple JW, Freedman J. Abnormal cellular immune mechanisms associated with autoimmune thrombocytopenia. Transfus Med Rev. 1995 Oct;9(4):327-38. doi: 10.1016/s0887-7963(05)80080-x. No abstract available.
PubMed 8541715Karpatkin S. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet. 1997 May 24;349(9064):1531-6. doi: 10.1016/S0140-6736(96)12118-8. No abstract available.
PubMed 9167472George JN, el-Harake MA, Raskob GE. Chronic idiopathic thrombocytopenic purpura. N Engl J Med. 1994 Nov 3;331(18):1207-11. doi: 10.1056/NEJM199411033311807. No abstract available.
PubMed 7935660
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-Dose Cyclophosphamide With CD34+ Selected Autologous Hematopoietic Cell Support for Treatment of Refractory Chronic Autoimmune Thrombocytopenia
- ClinicalTrials.gov ID
- NCT00001630
- Acronym / sponsor ID
- 970154
- Keywords
- Immunosuppression, Thrombocytopenia, Autoimmune Disease, Evan's Syndrome, Autoimmune Hemolytic Anemia, Episodic Bleeding
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 21 Jul 1997
- Study completion
- 11 Jun 2009 (actual)
- First posted
- 4 Nov 1999 (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.
Platelets are particles found along with red and white blood cells in the blood that play a role in the process of blood clotting. Disorders affecting the platelets can lower the amount of platelets in the blood and put patients at risk of bleeding. The condition of low platelets is referred to as thrombocytopenia.
Thrombocytopenia can be associated with a variety of diseases including cancer, leukemia, tuberculosis, or as a result of an autoimmune reaction. Autoimmune reactions are disorders in which the normal immune system begins attacking itself. Autoimmune thrombocytopenia (AITP) is a disorder of low blood platelet counts in which platelets are destroyed by antibodies produced by the immune system.
Unfortunately, many patients with AITP do not respond to standard treatments for thrombocytopenia. Cyclophosphamide is a drug that works to suppress the activity of the immune system. Researchers believe that combining this drug with transplanted rescued blood stem cells may provide effective treatment for AITP.
The purpose of this study is to explore the affordability and safety of this therapy for the treatment of AITP. The effectiveness of the therapy will be measured by the number of patients whose platelet levels rise greater than 100,000/m3.
If this treatment approach appears affordable, this study will form the basis for a larger study to compare alternate treatment approaches.
Detailed description
Autoimmune Thrombocytopenia (AITP) is a disorder of low blood platelet counts in which platelet destruction is caused by antiplatelet autoantibodies. A large proportion of patients with chronic AITP are refractory to standard therapies including corticosteroids, immune globulin and splenectomy. Cyclophosphamide is a cytotoxic immunosuppressive agent which may induce durable remissions of refractory autoimmune diseases. High-dose cyclophosphamide with peripheral blood stem cell (PBPC) rescue has been proposed as a potential definitive therapy for AITP; however, the infusion of autoreactive lymphocytes could result in relapse. The use of PBPC depleted of T-lymphocytes could circumvent this limitation.
The purpose of this phase I/II study is to explore the feasibility and safety of this approach, and to seek preliminary evidence of effectiveness, of using high-dose cyclophosphamide (50 mg/kg/day x 4) followed by infusion of autologous PBPC enriched for CD34+ cells (concomitantly depleted of CD3+ cells) for the treatment of patients with refractory AITP. Safety/feasibility parameters to be examined will include the ability to mobilize, harvest and purify sufficient PBPC to yield greater than 2 x 10(6) CD34+ cells/kg; symptomatic acceptability and hematologic toxicities of the mobilization regimen (filgrastim 10 micrograms/kg/day IV); tolerability of the leukapheresis procedure, including the central line placement and maintenance; depth and duration of blood cell nadirs following chemotherapy; peritransplant bleeding episodes and transfusion requirements; episodes of febrile neutropenia, culture-proven infections and antibiotic usage. Effectiveness will be gauged by the rapidity and number of patients to achieve complete remission (platelet count greater than 100,000/mm(3) and partial remission (platelet count greater than 50,000/mm(3) or doubling of the platelet count with resolution of bleeding episodes). Ancillary evidence of therapeutic effect will be sought by examining changes in titers of platelet surface glycoprotein antibodies. In addition, alterations in T-lymphocyte subsets will be examined by flow cytometry. If this treatment approach appears feasible, this study will form the basis for a larger trial to compare alternate treatment approaches.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Male or female, ages 18-65 years old.
- Refractory severe chronic autoimmune thrombocytopenia, with or without autoimmune hemolytic anemia (Evan's syndrome), with all the following:
- Platelet count frequently below 20,000/mm(3) despite active
- treatment for a period of greater than 6 months.
- Normal or increased megakaryocytes on bone marrow
Key exclusion criteria (13 listed)
- ECOG performance status greater than 1.
- History of coronary artery disease, angina pectoris or congestive heart failure.
- LV ejection fraction less than 40 percent by 2D echocardiogram.
- Renal disease, serum creatinine greater than 2.5 mg/dL or creatinine clearance less than 30 mL/min.
- Significant hepatic dysfunction, bilirubin greater than 2 mg/dL or transaminases greater than 2 times UNL.
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 |
|---|---|---|
| Isolex 300i | Device | – |
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 2 Jul 2017.
- Background: PubMed 8541715Semple JW, Freedman J. Abnormal cellular immune mechanisms associated with autoimmune thrombocytopenia. Transfus Med Rev. 1995 Oct;9(4):327-38. doi: 10.1016/s0887-7963(05)80080-x. No abstract available.
- Background: PubMed 9167472Karpatkin S. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet. 1997 May 24;349(9064):1531-6. doi: 10.1016/S0140-6736(96)12118-8. No abstract available.
- Background: PubMed 7935660George JN, el-Harake MA, Raskob GE. Chronic idiopathic thrombocytopenic purpura. N Engl J Med. 1994 Nov 3;331(18):1207-11. doi: 10.1056/NEJM199411033311807. No abstract available.
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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 Isolex 300i in people with Autoimmune Disease and Autoimmune Hemolytic Anemia, run by National Heart, Lung, and Blood Institute (NHLBI) 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 17 inclusion and 13 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 2 Jul 2017. 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 NCT00001630, 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 2 Jul 2017.