Treatment of Autoimmune Thrombocytopenia (AITP)
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|ClinicalTrials.gov Identifier: NCT00001630|
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : July 2, 2017
|First Submitted Date ICMJE||November 3, 1999|
|First Posted Date ICMJE||November 4, 1999|
|Last Update Posted Date||July 2, 2017|
|Study Start Date ICMJE||July 21, 1997|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Treatment of Autoimmune Thrombocytopenia (AITP)|
|Official Title ICMJE||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.
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.
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 Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
|Intervention ICMJE||Device: Isolex 300i|
|Study Arms ICMJE||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date ICMJE||June 11, 2009|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
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:
i. conventional-dose steroids (e.g., prednisone or dosage of 40
mg/day or equivalent, followed by dosage taper) for at least 3
ii. intravenous immunoglobulin.
e. Episodic bleeding requiring transfusions or ecchymoses interfering
with ordinary daily activities.
ECOG performance status greater than 1.
Cardiopulmonary disease including:
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.
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).
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.
|Ages ICMJE||18 Years to 65 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00001630|
|Other Study ID Numbers ICMJE||970154
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||March 21, 2011|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP