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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00306670
• Date of registration: 23/03/2006
• Prospective Registration: Yes
• Primary sponsor: Georgetown University
• Public title: Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Acquired Hemophilia A
• Scientific title: 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
• Date of first enrolment: April 2006
• Target sample size: 2
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00306670
• Study type: Interventional
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• Name: Craig Kessler, MD
• Affiliation: Georgetown University Hospital

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hemophilia A

Intervention(s)

Drug: prednisone

Drug: Rituxan

Primary Outcome(s)

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.]

Secondary ID(s)

U2688

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genentech, Inc.

Results

• Results available: Yes
• Date Posted: 10/02/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00306670