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Treating Patients With Recurrent PCNSL With Carboplatin/BBBD and Adding Rituxan To The Treatment Regimen

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00074165
Recruitment Status : Terminated (Lack of accrual)
First Posted : December 11, 2003
Results First Posted : November 16, 2011
Last Update Posted : April 21, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Edward Neuwelt, OHSU Knight Cancer Institute

Tracking Information
First Submitted Date  ICMJE December 10, 2003
First Posted Date  ICMJE December 11, 2003
Results First Submitted Date  ICMJE October 10, 2011
Results First Posted Date  ICMJE November 16, 2011
Last Update Posted Date April 21, 2017
Study Start Date  ICMJE January 2003
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 21, 2011)
Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years. [ Time Frame: 2 years ]
Per RECIST criteria (v1.1) and assessed by magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 21, 2011)
  • Number of Participants With Overall Survival Assessed by Clinical and Radiographic Response [ Time Frame: 5 years ]
    Overall survival is measured from entry onto study until death from any cause or until death or progression of disease, respectively.
  • Progression-free Survival Assessed by Clinical and Radiographic Response From First Day of Treatment Until Tumor Progression [ Time Frame: 5 years ]
  • Quality of Life Assessed by EORTC QOL Before Treatment and Then Every 3 Months [ Time Frame: 5 years ]
  • Ototoxicity Assessed by Audiology Hearing Test Done Monthly During Treatment [ Time Frame: 2 years ]
  • Effect of Sodium Thiosulfate (STS) on Granulocytes and Erythrocytes Assessed by Complete Blood Count Lab Values Done Weekly During Treatment [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treating Patients With Recurrent PCNSL With Carboplatin/BBBD and Adding Rituxan To The Treatment Regimen
Official Title  ICMJE A Phase II Trial Involving Patients With Recurrent PCNSL Treated With Carboplatin/BBBD, by Adding Rituxan (Rituximab), An Anti CD-20 Antibody, To The Treatment Regimen
Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as carboplatin, cyclophosphamide, etoposide, etoposide phosphate, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Osmotic blood-brain barrier disruption uses certain drugs to open the blood vessels around the brain and allow anticancer substances to be delivered directly to the brain tumor. Chemoprotective drugs such as sodium thiosulfate may protect normal cells from the side effects of carboplatin-based chemotherapy. Combining rituximab with chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining rituximab with combination chemotherapy given with osmotic blood-brain barrier disruption plus sodium thiosulfate in treating patients who have refractory or recurrent primary CNS lymphoma.

Detailed Description

OBJECTIVES:

Primary

  • Determine the efficacy of rituximab, carboplatin, cyclophosphamide, etoposide or etoposide phosphate and cytarabine administered in conjunction with osmotic blood-brain barrier disruption and high-dose sodium thiosulfate, in terms of complete response rate, in patients with refractory or recurrent primary CNS lymphoma.

Secondary

  • Determine the overall survival and 2-year progression-free survival of patients treated with this regimen.
  • Determine the quality of life and cognitive function of patients treated with this regimen.
  • Determine the neurotoxicity of this regimen in these patients.
  • Determine the percentage of patients with ototoxicity over time after treatment with this regimen.
  • Determine the effect of delayed administration of sodium thiosulfate on granulocyte and erythrocyte counts in these patients.

OUTLINE: This is a multicenter study.

Patients receive rituximab IV on day 1. On days 2 and 3, patients receive carboplatin intra-arterially over 10 minutes, cyclophosphamide IV over 10 minutes, and etoposide or etoposide phosphate IV over 10 minutes in conjunction with blood-brain barrier disruption. Patients also receive high-dose sodium thiosulfate IV over 15 minutes administered 4 and 8 hours after carboplatin on days 2 and 3 and intraventricular or intrathecal cytarabine on day 14. Beginning 48 hours after the last dose of chemotherapy, patients receive filgrastim (G-CSF)* subcutaneously (SC) daily for 7-10 days or until blood counts recover. Treatment repeats every 4 weeks for up to 12 courses.

NOTE: * Alternatively, patients may receive a single dose of pegfilgrastim SC, administered 48 hours after the completion of chemotherapy

Patients with intraocular lymphoma also receive methotrexate intravitreally twice weekly until the vitreous is clear of cells by slit lamp exam; once weekly for 1 month; and then monthly for 1 year.

Quality of life is assessed at baseline, every 3 months during treatment, within 30 days of final treatment, then every 6 months for 1 year, and then annually thereafter.

Patients are followed monthly for 3 months, every 2 months for 8 months, every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 11-25 patients will be accrued for this study within 7-10 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain and Central Nervous System Tumors
  • Drug/Agent Toxicity by Tissue/Organ
  • Lymphoma
  • Thrombocytopenia
Intervention  ICMJE
  • Drug: Rituxan
    Total dose: 375mg/m2 infused IV; Every 4 weeks for up to one year.
    Other Name: Rituximab
  • Drug: Cyclophosphamide
    Dose 330mg/m2 x 2 days infused IV; Every 4 weeks for up to 1 year
  • Drug: Etoposide
    Dose 200mg/m2 x 2 days infused IV; Every 4 weeks for up to one year. Etoposide phosphate may be given instead.
  • Drug: Etoposide phosphate
    Dose 200mg/m2 infused IV x 2 days; Every 4 weeks for up to one year. Etoposide may be given instead.
  • Drug: Carboplatin
    Dose: 200mg/m2 x 2 days infused IA with BBBD; Every 4 weeks for up to one year.
  • Drug: Sodium thiosulfate

    Dose: 4 hrs post carboplatin = 20gm/m2;

    Dose: 8 hrs post carboplatin = 16gm/m2

    Infused IV x 2 days

    Other Name: STS
  • Drug: Neupogen
    48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. Neulasta (Pegfilgrastim) may be given instead.
    Other Names:
    • G-CSF
    • filgrastim
  • Drug: Neulasta
    Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead.
    Other Name: Pegfilgrastim
  • Drug: Cytarabine
    Dose: 40mg on Day 14 following chemotherapy
Study Arms  ICMJE Experimental: All subjects
Interventions:
  • Drug: Rituxan
  • Drug: Cyclophosphamide
  • Drug: Etoposide
  • Drug: Etoposide phosphate
  • Drug: Carboplatin
  • Drug: Sodium thiosulfate
  • Drug: Neupogen
  • Drug: Neulasta
  • Drug: Cytarabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 10, 2011)
17
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE December 2010
Actual Primary Completion Date June 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA:

  • Signed informed consent form in accordance with institutional guidelines
  • Histologically or cytologically confirmed primary CNS lymphoma documented by brain biopsy or cerebrospinal fluid or vitrectomy analysis
  • CD20 positive disease
  • Progressive or relapsed disease during or after completion of prior methotrexate-based chemotherapy
  • Aged 18 months to 75 years
  • Performance status ECOG 0-3 OR Karnofsky 30-100%
  • Hematocrit at least 25% (transfusion or epoetin alfa allowed)
  • Absolute granulocyte count at least 1,200/mm^3
  • Platelet count at least 100,000/mm^3 OR at least lower limit of normal
  • Bilirubin no greater than 2.0 times upper limit of normal
  • Creatinine less than 1.8 mg/dL
  • Calculated Creatinine clearance (CrCl) at least 50 mL/min
  • Adequate cardiac function to tolerate general anesthesia
  • Adequate pulmonary function to tolerate general anesthesia
  • Available for follow-up for 1 year post therapy
  • Fertile patients must use effective contraception for a minimum of 2 months before and during study participation

EXCLUSION CRITERIA:

  • Radiographic signs of intra-cranial herniation and/or spinal block
  • HIV positive
  • Systemic lymphoma
  • Positive serum HCG, pregnant or lactating
  • Allergy to study agents
  • Hepatitis B or hepatitis C positive
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Months to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00074165
Other Study ID Numbers  ICMJE IRB00000641
5R01CA137488-15 ( U.S. NIH Grant/Contract )
ONC-02059-LX ( Other Identifier: OHSU Knight Cancer Institute )
641 ( Other Identifier: OHSU eIRB )
7465 ( Other Identifier: OHSU IRB (discontinued number) )
OHSU-641 ( Other Identifier: OHSU IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Edward Neuwelt, OHSU Knight Cancer Institute
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE OHSU Knight Cancer Institute
Original Study Sponsor  ICMJE Oregon Health and Science University
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Edward A. Neuwelt, MD OHSU Knight Cancer Institute
PRS Account OHSU Knight Cancer Institute
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP