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

NCT00306670 | Terminated Phase 2 Results

• 1 other identifier: U2688
• Study Type: interventional
• Target: 2
• Locations: 0 countries
• Sites: N/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.

Conditions

Hemophilia A

Keywords

Acquired Hemophilia A; Anti-Factor VIII antibodies; Anti-Factor VIII inhibitors; Hemophilia A; Factor VIII inhibitors

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  When 25 patients have completed the study.

Study Arms (2)

Rituximab

EXPERIMENTAL

Patients will receive rituximab.

Drug: Rituxan; Drug: prednisone

Oral cyclophosphamide

ACTIVE COMPARATOR

Patients will receive oral cyclophosphamide.

Drug: prednisone

Interventions

Rituxan DRUG

Acquired Hemophilia A Patients Who Have Developed Anti-Factor VIII Antibodies

Also known as: Rituximab

Rituximab

prednisone DRUG

\<30 mg/day

Also known as: corticosteroids

Oral cyclophosphamide; Rituximab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Georgetown University: lead
• Genentech, Inc.: collaborator

MeSH Terms

Conditions

Hemophilia A; Factor 8 deficiency, acquired

Interventions

Rituximab; Prednisone; Adrenal Cortex Hormones

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

Sponsor terminated study prior to patient receiving first dose of study drug.

Results Point of Contact

• Title: Craig M Kessler, MD
• Organization: Georgetown University

kesslerc@georgetown.edu

202-444-8676

Study Officials

• Craig Kessler, MD

  Georgetown University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 23, 2006
• First Posted: March 24, 2006
• Study Start: April 1, 2006
• Primary Completion: January 1, 2011
• Study Completion: August 1, 2011
• Last Updated: February 10, 2017
• Results First Posted: February 10, 2017

Record last verified: 2016-12