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

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ClinicalTrials.gov Identifier: NCT00306670
Recruitment Status : Terminated (Sponsor no longer funding study.)
First Posted : March 24, 2006
Results First Posted : February 10, 2017
Last Update Posted : February 10, 2017
Genentech, Inc.
Information provided by (Responsible Party):
Craig Kessler, Georgetown University

Tracking Information
First Submitted Date  ICMJE March 23, 2006
First Posted Date  ICMJE March 24, 2006
Results First Submitted Date  ICMJE December 20, 2016
Results First Posted Date  ICMJE 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
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
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  ICMJE 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  ICMJE
  • Experimental: Rituximab
    Patients will receive rituximab.
    • 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)
Original Enrollment  ICMJE
 (submitted: March 23, 2006)
Actual Study Completion Date  ICMJE 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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE 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  ICMJE Not Provided
Current Responsible Party Craig Kessler, Georgetown University
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE Georgetown University
Original Study Sponsor  ICMJE Same as current
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