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Treatment of Autoimmune Thrombocytopenia (AITP)

Primary Purpose

Autoimmune Disease, Autoimmune Hemolytic Anemia, Thrombocytopenia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Isolex 300i
Sponsored by
National Heart, Lung, and Blood Institute (NHLBI)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autoimmune Disease focused on measuring Immunosuppression, Thrombocytopenia, Autoimmune Disease, Evan's Syndrome, Autoimmune Hemolytic Anemia, Episodic Bleeding

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA: 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. No plausible alternative etiology such as drug-mediated thrombocytopenia, marrow failure syndrome or thrombocytopenia related to viral or bacterial infection. Failure of treatment with: i. conventional-dose steroids (e.g., prednisone or dosage of 40 mg/day or equivalent, followed by dosage taper) for at least 3 months. ii. intravenous immunoglobulin. iii. splenectomy. e. Episodic bleeding requiring transfusions or ecchymoses interfering with ordinary daily activities. EXCLUSION CRITERIA: 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. 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.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 3, 1999
Last Updated
June 30, 2017
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT00001630
Brief Title
Treatment of Autoimmune Thrombocytopenia (AITP)
Official Title
High-Dose Cyclophosphamide With CD34+ Selected Autologous Hematopoietic Cell Support for Treatment of Refractory Chronic Autoimmune Thrombocytopenia
Study Type
Interventional

2. Study Status

Record Verification Date
March 21, 2011
Overall Recruitment Status
Completed
Study Start Date
July 21, 1997 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 11, 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autoimmune Disease, Autoimmune Hemolytic Anemia, Thrombocytopenia
Keywords
Immunosuppression, Thrombocytopenia, Autoimmune Disease, Evan's Syndrome, Autoimmune Hemolytic Anemia, Episodic Bleeding

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
29 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Device
Intervention Name(s)
Isolex 300i

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA: 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. No plausible alternative etiology such as drug-mediated thrombocytopenia, marrow failure syndrome or thrombocytopenia related to viral or bacterial infection. Failure of treatment with: i. conventional-dose steroids (e.g., prednisone or dosage of 40 mg/day or equivalent, followed by dosage taper) for at least 3 months. ii. intravenous immunoglobulin. iii. splenectomy. e. Episodic bleeding requiring transfusions or ecchymoses interfering with ordinary daily activities. EXCLUSION CRITERIA: 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. 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.
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8541715
Citation
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.
Results Reference
background
PubMed Identifier
9167472
Citation
Karpatkin S. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet. 1997 May 24;349(9064):1531-6. doi: 10.1016/S0140-6736(96)12118-8. No abstract available.
Results Reference
background
PubMed Identifier
7935660
Citation
George 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.
Results Reference
background

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Treatment of Autoimmune Thrombocytopenia (AITP)

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