Higher Dose of Rituxan Versus Standard Doses of Rituxan With Cyclophosphamide, Vincristine, and Prednisone in Subjects With Chronic ITP

NCT00774202 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 0301005964
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Immune Thrombocytopenic Purpura

Keywords

Pts w/ Chronic ITP who have fail/relap after Rituxan rx

Outcome Measures

Primary Outcomes (1)

• Efficacy of Higher Double Doses of Rituxan and of Standard Dose of Rituxan + Cyclophosphamide, Vincristine, Prednisone

  Outcome measure was determined by comparing the study participants' historical responses to their initial treatment of rituximab at standard dose/regimen without "enhancement" (based on duration of response and type of response) to the participants response to their study treatment responses. Thus each patient was his or her own control although all study treatments included standard dose rituximab treatments (one at double the dose and one with additional treatments).

  2 years

Secondary Outcomes (2)

• Number of Participants With SAEs

  2 years

• Relative Efficacy of the 2 Groups

  2 years

Study Arms (2)

Rituximab, Cyclophosphamide, Vincristine, Prednisone

ACTIVE COMPARATOR

'Standard Dose of Rituximab administered with C, V, P (CVP)' Interventions: Rituximab will be administered as an IV infusion at the standard dose of 375 mg/m2 for 4 doses at standard rates and use of premedication. The schedule will be to give the first rituximab infusion 5 days (± 3 days) prior to first administration of CVP, and the following 3 infusions will be given on the same day as the 3 cycles of C, V, P. On those days, the IV Cyclophosphamide and Vincristine will be given first so that the administration of fluids with the rituximab can be used as post-cyclophosphamide hydration, Cyclophosphamide dosing will be 750mg/m2 (maximum 2000mg), vincristine 1.4 mg/m2 (up to 1.6 mg), prednisone 100mg po daily for 5 days.

Drug: Rituxan, Cyclophosphamide, Vincristine, Prednisone

Higher Dose of Rituximab

ACTIVE COMPARATOR

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 the Q-T interval.

Drug: Higher Dose of Rituximab

Interventions

Rituxan, Cyclophosphamide, Vincristine, Prednisone DRUG

'Rituximab, Cyclophosphamide, Vincristine, Prednisone interventions are as follows: 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 infusions of C and V and oral P, and the following 3 rituximab infusions will be given on the same day as the 3 cycles of C, V, and P.

Also known as: Rituximab

Rituximab, Cyclophosphamide, Vincristine, Prednisone

Higher Dose of Rituximab DRUG

rituximab 750mg/m2 (twice the standard dose of 375mg/m2) will be given weekly for 4 weeks. Premedication and infusion rate escalation will be exactly the same as for standard dose rituximab. The additional dose will thus run at 400ml/hr.

Higher Dose of Rituximab

Eligibility Criteria

• Age: 12 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• Male and Female
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Biogen: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

525 East 68th Street

New York, New York, 10065, United States

Location

Related Publications (1)

• Hasan A, Michel M, Patel V, Stasi R, Cunningham-Rundles S, Leonard JP, Bussel J. Repeated courses of rituximab in chronic ITP: Three different regimens. Am J Hematol. 2009 Oct;84(10):661-5. doi: 10.1002/ajh.21512.

  PMID: 19731307 RESULT

Related Links

• http://onlinelibrary.wiley.com/doi/10.1002/ajh.21512/epdf

MeSH Terms

Conditions

Purpura, Thrombocytopenic, Idiopathic

Interventions

Rituximab; Cyclophosphamide; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Purpura, Thrombocytopenic; Purpura; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia; Hemorrhagic Disorders; Autoimmune Diseases; Immune System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: James B. Bussel, M.D. Professor of Pediatrics
• Organization: Weill Cornell Medical College

jbussel@med.cornell.edu

212-746-3474

Study Officials

• James B Bussel, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: October 17, 2008
• Study Start: November 1, 2003
• Primary Completion: February 1, 2008
• Study Completion: February 1, 2008
• Last Updated: January 9, 2019
• Results First Posted: November 14, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: soon (2009)
• Access Criteria: journal subscribers

Locations

US (1)