High-Dose Cyclophosphamide With CD34+ Selected Autologous Hematopoietic Cell Support for Treatment of Refractory Chronic Autoimmune Thrombocytopenia
Isolex 300i
Cytopenia+7
+ Anemia
+ Anemia, Hemolytic
Treatment Study
Summary
Study start date: July 21, 1997
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.29 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 65 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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.
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, United StatesOpen National Institutes of Health Clinical Center, 9000 Rockville Pike in Google Maps