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

NCT00074165 | Terminated Phase 2 Results DMC

• 6 other identifiers: IRB000006415R01CA137488-15ONC-02059-LX6417465OHSU-641
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

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.

Conditions

Brain and Central Nervous System Tumors; Drug/Agent Toxicity by Tissue/Organ; Lymphoma; Thrombocytopenia

Keywords

drug/agent toxicity by tissue/organ; thrombocytopenia; intraocular lymphoma; primary central nervous system non-Hodgkin lymphoma; primary central nervous system Hodgkin lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years.

  Per RECIST criteria (v1.1) and assessed by magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions.

  2 years

Secondary Outcomes (5)

• Number of Participants With Overall Survival Assessed by Clinical and Radiographic Response

  5 years

• Progression-free Survival Assessed by Clinical and Radiographic Response From First Day of Treatment Until Tumor Progression

  5 years

• Quality of Life Assessed by EORTC QOL Before Treatment and Then Every 3 Months

  5 years

• Ototoxicity Assessed by Audiology Hearing Test Done Monthly During Treatment

  2 years

• Effect of Sodium Thiosulfate (STS) on Granulocytes and Erythrocytes Assessed by Complete Blood Count Lab Values Done Weekly During Treatment

  2 years

Study Arms (1)

All subjects

EXPERIMENTAL

Drug: Rituxan; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Etoposide phosphate; Drug: Carboplatin; Drug: Sodium thiosulfate; Drug: Neupogen; Drug: Neulasta; Drug: Cytarabine

Interventions

Rituxan DRUG

Total dose: 375mg/m2 infused IV; Every 4 weeks for up to one year.

Also known as: Rituximab

All subjects

Cyclophosphamide DRUG

Dose 330mg/m2 x 2 days infused IV; Every 4 weeks for up to 1 year

All subjects

Etoposide DRUG

Dose 200mg/m2 x 2 days infused IV; Every 4 weeks for up to one year. Etoposide phosphate may be given instead.

All subjects

Etoposide phosphate DRUG

Dose 200mg/m2 infused IV x 2 days; Every 4 weeks for up to one year. Etoposide may be given instead.

All subjects

Carboplatin DRUG

Dose: 200mg/m2 x 2 days infused IA with BBBD; Every 4 weeks for up to one year.

All subjects

Sodium thiosulfate DRUG

Dose: 4 hrs post carboplatin = 20gm/m2; Dose: 8 hrs post carboplatin = 16gm/m2 Infused IV x 2 days

Also known as: STS

All subjects

Neupogen DRUG

48 hours after chemotherapy, QD x 7-10 days until WBC greater than 5000. Neulasta (Pegfilgrastim) may be given instead.

Also known as: G-CSF, filgrastim

All subjects

Neulasta DRUG

Dose: 6mg, 24-72 hours after chemotherapy. Neupogen may be given instead.

Also known as: Pegfilgrastim

All subjects

Cytarabine DRUG

Dose: 40mg on Day 14 following chemotherapy

All subjects

Eligibility Criteria

• Age: 18 Months - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Good Samaritan Hospital Cancer Treatment Center, Hatton Institute

Cincinnati, Ohio, 45220, United States

Location

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Drug-Related Side Effects and Adverse Reactions; Lymphoma; Thrombocytopenia; Intraocular Lymphoma

Interventions

Rituximab; Cyclophosphamide; Etoposide; etoposide phosphate; Carboplatin; sodium thiosulfate; Filgrastim; Granulocyte Colony-Stimulating Factor; pegfilgrastim; Cytarabine

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Chemically-Induced Disorders; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Blood Platelet Disorders; Hematologic Diseases; Cytopenia; Eye Neoplasms

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; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Coordination Complexes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Dr. Edward Neuwelt
• Organization: OHSU Knight Cancer Institute

neuwelte@ohsu.edu

503-494-5626

Study Officials

• Edward A. Neuwelt, MD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 10, 2003
• First Posted: December 11, 2003
• Study Start: January 1, 2003
• Primary Completion: June 1, 2010
• Study Completion: December 1, 2010
• Last Updated: July 6, 2023
• Results First Posted: November 16, 2011

Record last verified: 2023-06

Locations

US (2)