A Trial to Treat Patients With ITP Who Do Not Achieve a Durable Response to Rituxan Alone
Study Details
Study Description
Brief Summary
The purpose of this research study is to compare the efficacy and safety of higher doses of rituximab to a combination of standard doses of Rituxan + CVP (Cyclophosphamide, Vincristine, and Prednisone) in patients with chronic Idiopathic Thrombocytopenic Purpura (ITP who did not respond to or relapsed after standard doses of rituximab.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
Primary Objectives
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Efficacy: The primary objective (primary endpoint) is to determine the rate of response (partial or complete response) at week 16 (± 2) post-treatment in both pilot arms: the high dose Rituximab (or HDR) group (750 mg/m2 x 4) and the group treated with a regimen combining standard doses of Rituximab with CVP (R-CVP.) A complete response (CR) will be a platelet count increase ³ 150,000/mL on two consecutive occasions one week apart, without any other therapy. A partial response will be considered if the platelet count increases between 50 and 150,000/mL.
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Safety: To assess and compare the incidence of moderate and severe adverse-events including the number and type of infections in both arms of the study using Genentech standard safety monitoring and serious adverse event (SAE) reporting.
Secondary Objectives
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To compare the response rate in the 2 treatment arms in the "Rituximab non-responders" sub group (see 4.1 for definition)
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To compare the response rate in the 2 treatment arms in the " Rituximab relapsers" subgroup
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To assess the mean duration of response (PR or CR) in the 2 treatment arms.
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To evaluate the duration of very low to absent peripheral blood B cells in the two treatment arms.
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To assess the incidence of hypogammaglobulinemia (IgG and/or IgM level < ½ of lower limit of normal for age) and white blood counts in the two arms.
Study Design
Outcome Measures
Primary Outcome Measures
Eligibility Criteria
Criteria
Inclusion Criteria:
Patients will be eligible to participate in the study if they:
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Have chronic ITP19 (> 6 months duration).
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Have received Rituximab a minimum of 3 months prior to entry.
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Have received no more than 2 courses of Rituximab at standard dose separated by a minimum of 12 weeks.
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Have not achieved a durable response to Rituximab, with platelet counts < 30,000/ml when not supported by other treatment.
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Have a platelet count of < 30,000/ul on two separate occasions 1-2 weeks apart within the past month prior to the inclusion.
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Are age ≥ 12 years old.
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Had a splenectomy at least 60 days prior to study entry, or a contraindication to splenectomy.
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Give written informed consent.
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Use an effective means of contraception during treatment and for six months after completion of treatment.
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Have negative serum pregnancy test, for all women who are able to have children, within 14 days prior to study entry.
Exclusion Criteria:
Male and female subjects will be ineligible to participate if they:
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Received prior treatment with cyclophosphamide within the last 3 months.
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Received prior treatment with > 4 infusions of vinca alkaloids within the 6 months.
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Had previous or concomitant malignancy other than basal cell or squamous cell carcinoma of the skin, carcinoma-in-situ of the cervix, or other malignancy for which the patient had not been disease-free for at least 5 years.
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Have an HIV infection.
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Have hepatitis Bs antigen positivity or active hepatitis C infection
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Have an absolute neutrophil count < 1.000/mm3 at study entry (unless related to autoimmune neutropenia).
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Have a Hemoglobin level < 10 g/dl other than caused by thalassemia trait, iron deficiency or autoimmune hemolytic anemia (patients with Evan's syndrome will not be excluded).
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Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL.
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Have an inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/or an AST or ALT level > 3x upper limit of normal.
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Have active infection requiring antibiotic therapy within 7 days prior to study entry.
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Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug.
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Have had a prior severe reaction to Rituximab, leading to discontinuation of treatment.
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Have a New York Heart Classification III or IV heart disease.
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Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Weill Medical College of Cornell University Division of Pediatric Hematology-Oncology | New York | New York | United States | 10021 |
Sponsors and Collaborators
- Weill Medical College of Cornell University
- Genentech, Inc.
Investigators
- Principal Investigator: James B Bussel, M.D., Weill Medical College of Cornell University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- U2735S