Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Acquired Hemophilia A

Tracking Information
First Submitted Date ICMJE	March 23, 2006
First Posted Date ICMJE	March 24, 2006
Results First Submitted Date	December 20, 2016
Results First Posted Date	February 10, 2017
Last Update Posted Date	February 10, 2017
Study Start Date ICMJE	April 2006
Actual Primary Completion Date	January 2011 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: December 20, 2016)	To Evaluate the Total Number of Circulating Lymphocytes and Lymphocyte Phenotypes and to Correlate With the Effectiveness of Rituximab and Oral Cyclophosphamide to Achieve and Preserve Complete Eradication of the Refractory Autoantibody. [ Time Frame: When 25 patients have completed the study. ]; the 2 recruited patients did not eradicate their inhibitors with 3 weeks of corticosteroids and did not progress in clinical trial since funding was eliminated and study terminated
Original Primary Outcome Measures ICMJE; (submitted: March 23, 2006)	To Evaluate the Total Number of Circulating Lymphocytes and Lymphocyte Phenotypes and to Correlate With the Effectiveness of Rituximab and Oral Cyclophosphamide to Achieve and Preserve Complete Eradication of the Refractory Autoantibody.
Change History	Complete list of historical versions of study NCT00306670 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Acquired Hemophilia A
Official Title ICMJE	A Prospective, Phase II/III Randomized, Mult-institutional Controlled, Open-label, Phase II Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Patients With Acquired Hemophilia A
Brief Summary	The purpose of this study is to evaluate the rate of response when administering rituximab to suppress or eliminate the anti-body in a patient's blood that inhibits the effectiveness of their factor replacement product compared to treatment using cyclophosphamide. This is a Phase 2/3 study to find out what effects (good and bad) and response rituximab has on a patient and their anti-Factor VIII antibodies. Also, to compare the effect (good and bad) of the rituximab with cyclophosphamide on a patient and their anti-Factor VIII antibodies to see which is better. This research is being done because we do not know which treatment regimen (rituximab or cyclophosphamide) is more effective in eliminating or suppressing the anti-Factor VIII antibody in patients with acquired Hemophilia A.
Detailed Description	This is a prospective Phase II randomized multi-institutional controlled pilot trial comparing the regimen of single agent rituximab with 6 weeks cytotoxic therapy with oral cyclophosphamide to eradicate or suppress autoimmune anti-factor VIII antibodies in individuals with acquired hemophilia A. Patients will be randomized to receive either of these two regimens when their autoimmune anti-factor VIII antibodies prove to be refractory to initial upfront immunosuppressive treatment with oral prednisone 1 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks. Patients will be randomized to the treatment cohorts according to the biostatistical methods.
Study Type ICMJE	Interventional
Study Phase	Phase 2; Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Hemophilia A
Intervention ICMJE	Drug: Rituxan Acquired Hemophilia A Patients Who Have Developed Anti-Factor VIII Antibodies Other Name: Rituximab; Drug: prednisone <30 mg/day Other Name: corticosteroids
Study Arms	Experimental: Rituximab Patients will receive rituximab. Interventions: Drug: Rituxan Drug: prednisone; Active Comparator: Oral cyclophosphamide Patients will receive oral cyclophosphamide. Intervention: Drug: prednisone
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Terminated
Actual Enrollment ICMJE; (submitted: November 5, 2009)	2
Original Enrollment ICMJE; (submitted: March 23, 2006)	25
Actual Study Completion Date	August 2011
Actual Primary Completion Date	January 2011 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Diagnosis of acquired hemophilia A in a previously non-coagulopathic individual.; Prior treatment with at least 3 weeks of immunosuppressive therapy; Factor VIII: C levels <50% within 14 days prior to study entry, which do not correct in coagulation assays in which normal plasma is mixed and incubated with patient plasma.; Measurable anti-factor VIII:C antibody inhibitor activity > 0.6 Bethesda Units/ml.; Age ³18 years; Written informed consent; Use of an effective means to avoid pregnancy, including abstinence, for women of childbearing potential,.; Serum bilirubin less than or equal to the upper limit of normal (ULN); ALT and AST £2.5´ ULN within 14 days prior to study entry; Serum creatinine £1.5´ the ULN within 14 days prior to study entry; Negative serum pregnancy test, for all women of childbearing potential, within 14 days prior to study entry Exclusion Criteria: Continued treatment requirement of prednisone ≥30mg/day or equivalent dosing of other corticosteroid preparations to control serious symptoms of an underlying autoimmune disease state.; Treatment with cyclophosphamide, danazol, vinca alkaloids, azathioprine, IVIG, or other immunosuppressive, immunomodulatory, or cytotoxic agents (other than decreasing doses of corticosteroids) within 30 days prior to study entry.; Anticipated need for repeated extracorporeal plasmapheresis in order to reverse refractory bleeding associated with acquired hemophilia.; Treatment with other experimental agents within 30 days prior to study entry; Known sensitivity to murine or chimeric products; Hepatitis BsAg positivity or high risk for reactivation of Hepatitis B.; Active infection requiring antibiotic therapy within 7 days prior to study entry; Current use of any required medications, which in the opinion of the treating physician, could be inducing the formation of auto-FVIII:C inhibitory antibodies; Prior treatment with rituximab or other monoclonal antibody therapy; Known HIV antibody positivity; NCI-CTC Grade ³1 cardiac arrhythmia ( refer to CTC v3); Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications; Currently pregnant women, lactating women, or women within 12 months of delivery, spontaneous miscarriage, or therapeutic or elective termination of pregnancy.; Known severe leucopenia (absolute neutrophil count <1000/µL) or thrombocytopenia (<25,000/µL);; Known pre-existing cystitis or severe urinary outflow obstruction.; Known history of recurrent severe opportunistic infections, eg. generalized herpes zoster;; Inability or unwillingness to comply with study design and requirements and follow-up procedures.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 65 Years (Adult)
Accepts Healthy Volunteers	Yes
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Not Provided
Removed Location Countries	United States
Administrative Information
NCT Number ICMJE	NCT00306670
Other Study ID Numbers ICMJE	U2688
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Craig Kessler, Georgetown University
Study Sponsor ICMJE	Georgetown University
Collaborators ICMJE	Genentech, Inc.
Investigators ICMJE	Principal Investigator: Craig Kessler, MD Georgetown University Hospital
PRS Account	Georgetown University
Verification Date	December 2016
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP