Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00306670
Other study ID # U2688
Secondary ID
Status Terminated
Phase Phase 2/Phase 3
First received March 23, 2006
Last updated January 9, 2014
Start date April 2006
Est. completion date August 2011

Study information

Verified date January 2014
Source Georgetown University
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 2
Est. completion date August 2011
Est. primary completion date January 2011
Accepts healthy volunteers Accepts Healthy Volunteers
Gender Both
Age group 18 Years to 65 Years
Eligibility 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, immodulatory, 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Rituxan
Acquired Hemophilia A Patients Who Have Developed Anti-Factor VIII Antibodies
prednisone
<30 mg/day

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Georgetown University Genentech, Inc.

Outcome

Type Measure Description Time frame Safety issue
Primary 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. When 25 patients have completed the study. No
See also
  Status Clinical Trial Phase
Completed NCT03834727 - Characterizing the Impact and Treatment of Reproductive Tract Bleeding on Women and Post-menarchal Girls With Bleeding Disorders
Completed NCT03191799 - A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors Phase 3
Completed NCT01599819 - BAX 855 Dose-Escalation Safety Study Phase 1
Terminated NCT04541628 - Safety & Efficacy of Encapsulated Allogeneic FVIII Cell Therapy in Haemophilia A Phase 1/Phase 2
Completed NCT02847637 - A Clinical Trial to Evaluate Prophylactic Emicizumab Versus no Prophylaxis in Hemophilia A Participants Without Inhibitors Phase 3
Completed NCT04072237 - Study of Coagulation Faction VIIa Variant Marzeptacog Alfa (Activated) in Adult Subjects With Hemophilia Phase 1
Completed NCT04085458 - Study to Gain More Information on How Safe and Effective Jivi Works in Patients With Severe Hemophilia A (Post-marketing Investigation) Phase 4
Completed NCT04565236 - A Post Approval Commitment Study to Gain More Information on How Safe and Effective KOVALTRY is in Chinese Children, Adolescents /Adults With Severe Hemophilia A Phase 4
Recruiting NCT05987449 - A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A Phase 1/Phase 2
Active, not recruiting NCT04621916 - Preventing Inhibitor Recurrence Indefinitely Phase 4
Not yet recruiting NCT02888223 - Pharmacokinetic Study of SCT800 in Previously Treated Patients With Hemophilia A Phase 1
Completed NCT02528968 - National Study of a Pharmacokinetic-Focused Educational Package for Patients With Severe Haemophilia A N/A
Completed NCT02225483 - Phenotypic Heterogeneity in Hemophilia A: An Investigation of the Role of Platelet Function N/A
Completed NCT02199717 - An Institutional Pilot Study to Investigate Physical Activity Patterns in Boys With Hemophilia N/A
Completed NCT01217255 - Comparing the Burden of Illness of Hemophilia in the Developing and the Developed World
Terminated NCT00995046 - Individually Tailored Prophylaxis in Patients With Severe Hemophilia A N/A
Completed NCT00969319 - Effekt-2 - Efficacy and Safety of Long-term Treatment With KOGENATE® FS in Latin America N/A
Completed NCT00868530 - Study Evaluating On-Demand Treatment Of Xyntha In Chinese Subjects Phase 3
Completed NCT00839202 - Activity and Content of Factor VIII (FVIII) in Human Plasma: The Assessment of a Novel Immunoassay N/A
Completed NCT00629837 - Pharmacokinetics and Safety of a Single Intravenous Infusion of BAY 79-4980 Phase 1