Rituximab and Dexamethasone Followed by Mycophenolate Mofetil or Placebo in Patients With Immune Thrombocytopenia

• Status: Withdrawn
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The investigators will attempt to further increase the cure rate of ITP with medical therapy by providing maintenance therapy with Mycophenolate mofetil (MMF) to persistent/chronic ITP patients after treating them with induction therapy combining rituximab and dexamethasone. The investigators will randomly assign patients to MMF versus placebo in order to demonstrate safety (e.g., for infectious risk) and efficacy (platelet counts stably >50x109/L more than 1 year off therapy).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Weill Medical College of Cornell University
• Treatments: BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Mycophenolate mofetil; Mycophenolic Acid; Rituximab

Criteria

Inclusion Criteria:

• Male or female, greater than 18 years old

• Signed written informed consent obtained prior to study entry

• Immune Thrombocytopenia according to the American Society of Hematology guidelines, with other potential causes of thrombocytopenia excluded, platelets less than 30 x 109/L at study entry

• Have adequate renal and hepatic function (creatinine and bilirubin less than 2 x Upper Limit of Normal (ULN), aspartate aminotransferase and alanine aminotransferase less than 3 x ULN)

• No significant cytopenias (hemoglobin greater than10 g/dL without ongoing transfusional support, absolute neutrophil count greater than 1.0 x109/L at study entry).

• If on corticosteroids, receiving less than or equal to 20 mg/day prednisone (or equivalent) with no change of dose for at least 2 weeks prior to study entry. No more than two 4-day courses of Dexamethasone prior to study entry. If on danazol, no change of dose for at least 2 weeks prior to study entry. (Thrombopoietin receptor agonist treatment will be allowed until the end of 8th week on study if started prior to study entry)

• No treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half-lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study

• No prior treatment with anti-B-lymphocyte antigen cluster of differentiation antigen 20 monoclonal antibody at a total dose greater than 375mg/m2

• Screen for Hepatitis B and be negative for Hepatitis B surface antigen

• Human Immunodeficiency Virus negative

• No history of active hepatitis C infection or a past history hepatitis C (confirmed by negative anti- Hepatitis C Virus Antibody)

• No past history of tuberculosis

• No chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, or chronic chest infection with bronchiectasis

• No current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease meeting laboratory threshold limits per investigator discretion)

• No significant concurrent, uncontrolled medical condition including but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease, which in the opinion of the investigator may represent a risk for the patient. Have no past or current malignancy for 3 years (excluding nonmelanoma skin cancers, e.g., basal cell carcinoma (BCC) and carcinoma in situ of the cervix)

• Women of childbearing potential must have a negative pregnancy test at screening

• No history of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.

• No history of venous or arterial thromboembolism in the past year.

• No clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities

Exclusion Criteria:

• Pregnant or lactating women

• Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study or until at least 6 months after treatment. Women of childbearing potential must have a negative pregnancy test at screening. Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy will be excluded from study. Adequate contraception is defined as intrauterine device, tubal sterilization, patient's partner had a vasectomy or total abstinence. Other contraceptive methods include hormonal contraceptive pills. Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy will be excluded from the study as well.

• Immunosuppressive agents or ITP treatments or other experimental treatments for ITP within 2 weeks. Intravenous Immunoglobulin, anti-Rh(D) prior to first day of rituximab treatment

• Splenectomy or any other surgery within 4 weeks

• Red blood cell transfusion or hospitalization for bleeding within 4 weeks

• Concomitant anticoagulation therapy (warfarin, enoxaparin, dabigatran, rivaroxaban, apixaban, fondaparinux) or any platelet aggregation inhibitors including aspirin and clopidogrel (until platelets stable greater than 100x109/L)

• New York Heart Classification III or IV heart disease. Other severe cardiovascular or cardiopulmonary disease, including chronic obstructive pulmonary disease

• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations