Study of Higher Dose of Rituxan Versus Standard Doses of Rituxan With Cyclophosphamide, Vincristine, and Prednisone in Subjects With Chronic ITP - Full Text View

Purpose

This study is designed to compare the efficacy and safety of higher doses of Rituxan with a regimen combining standard doses of Rituxan + CVP in patients with chronic ITP who did not respond to or relapsed after standard doses of Rituxan. Patients eligible for this protocol will be stratified into two subgroups according to their initial response to Rituxan.

Condition	Intervention	Phase
Immune Thrombocytopenic Purpura	Drug: Rituxan and Cyclophosphamide, Vincristine and Prednisone Drug: Higher Dose of Rituximab	Phase 2 Phase 3

Study Type:	Interventional
Official Title:	A Randomized Trial Comparing Higher Doses of Rituximab (Rituxan) With Standard Doses of Rituxan in Combination With CVP (Cyclophosphamide, Vincristine, and Prednisone) in Patients With Chronic ITP Who Have Failed/Relapsed After Rituxan Treatment

Resource links provided by NLM:

Genetics Home Reference related topics: thrombotic thrombocytopenic purpura

MedlinePlus related topics: Steroids

Drug Information available for: Cyclophosphamide Prednisone Vincristine sulfate Rituximab

U.S. FDA Resources

Further study details as provided by Weill Medical College of Cornell University:

Study Start Date:	November 2003
Study Completion Date:	February 2008
Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Standard Dose of Rituxan and CVP Rituximab will be administered as an IV infusion at the standard dose of 375 mg/m2 for 4 doses. However, the schedule of the infusions will be different than the usual one: Rather than administrating the 4 doses once weekly, the first infusion will be given 5 days (± 3 days) prior to the first CVP, and the following 3 infusions will be given on the same day as the 3 cycles of CVP.	Drug: Rituxan and Cyclophosphamide, Vincristine and Prednisone
Active Comparator: Higher Dose of Rituximab In this arm, Rituximab will be administered at a dose of 750 mg/m2 once a week x 4 consecutive weeks (4 infusions in total). We will perform EKG monitor tracings before, during and after Rituxan infusions. This will be a single-lead tracing that will allow us to look at issues such as the Q-T interval.	Drug: Higher Dose of Rituximab

Arms

Assigned Interventions

Active Comparator: Standard Dose of Rituxan and CVP

Rituximab will be administered as an IV infusion at the standard dose of 375 mg/m2 for 4 doses. However, the schedule of the infusions will be different than the usual one: Rather than administrating the 4 doses once weekly, the first infusion will be given 5 days (± 3 days) prior to the first CVP, and the following 3 infusions will be given on the same day as the 3 cycles of CVP.

Drug: Rituxan and Cyclophosphamide, Vincristine and Prednisone

Active Comparator: Higher Dose of Rituximab

In this arm, Rituximab will be administered at a dose of 750 mg/m2 once a week x 4 consecutive weeks (4 infusions in total). We will perform EKG monitor tracings before, during and after Rituxan infusions. This will be a single-lead tracing that will allow us to look at issues such as the Q-T interval.

Drug: Higher Dose of Rituximab

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Eligibility

Ages Eligible for Study:	12 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients will be eligible to participate in the study if they:

Have chronic ITP19 (> 6 months duration)
Have received Rituximab a minimum of 3 months prior to entry
Have received no more than 2 courses of Rituximab at standard dose separated by a minimum of 12 weeks
Have not achieved a durable response to Rituximab, with platelet counts < 30,000/ml when not supported by other treatment
Have a platelet count of < 30,000/ul on two separate occasions 1-2 weeks apart within the past month prior to the inclusion
We will allow patients who do not have 2 platelet counts < 30,000 on two separate occasions 1-2 weeks apart in the past month, as long as they have either Evan's Syndrome or autoimmune neutropenia (have hemoglobin < 10 g/dL and reticulocytes > 4%, or an absolute neutrophil count < 1.0 K/uL twice within 1 month)
Are age ≥ 10 years old
Had a splenectomy at least 60 days prior to study entry, or a contraindication to splenectomy
Give written informed consent
Use an effective means of contraception during treatment and for six months after completion of treatment
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:

Received prior treatment with cyclophosphamide within the last 3 months
Received prior treatment with > 4 infusions of vinca alkaloids within the 6 months
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
Have a HIV infection
Have hepatitis Bs antigen positivity or active hepatitis C infection
Have an absolute neutrophil count < 1.000/mm3 at study entry (unless related to autoimmune neutropenia)
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)
Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL
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
Have active infection requiring antibiotic therapy within 7 days prior to study entry
Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug
Have had a prior severe reaction to Rituximab, leading to discontinuation of treatment
Have a New York Heart Classification III or IV heart disease
Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00774202

Locations

United States, New York
525 East 68th Street
New York, New York, United States, 10065

Sponsors and Collaborators

Weill Medical College of Cornell University

Biogen Idec

Genentech

Investigators

Principal Investigator:

James B Bussel, M.D.

Weill Medical College of Cornell University

More Information

No publications provided

Responsible Party:	James B. Bussel, M.D., Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:	NCT00774202 History of Changes
Other Study ID Numbers:	0301005964
Study First Received:	October 15, 2008
Last Updated:	December 22, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Weill Medical College of Cornell University:

Patients with Chronic Immune Thrombocytopenic Purpura who have failed/relapsed after Rituxan treatment

Additional relevant MeSH terms:

Purpura
Purpura, Thrombocytopenic
Purpura, Thrombocytopenic, Idiopathic
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhage
Pathologic Processes
Skin Manifestations
Signs and Symptoms
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Immune System Diseases
Hemorrhagic Disorders
Autoimmune Diseases

Cyclophosphamide
Rituximab
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 23, 2013