Study of High-Dose Rituximab With Temozolomide as Treatment for Primary Central Nervous System (CNS) Lymphoma

NCT02113007 | Terminated Phase 2 Results

• 1 other identifier: SCRI CNS 20
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 4

Brief Summary

This study will evaluate the safety and efficacy of high-dose rituximab combined with temozolomide in the treatment of patients with Primary Central Nervous System Lymphomas (PCNSL). This novel combination will be evaluated in PCNSL patients who are 60 years of age or older, or in patients 18 years or older who refuse methotrexate-based treatment.

Conditions

Primary Central Nervous System Lymphoma

Keywords

Lymphoma; CNS; rituximab; temozolomide

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Patients will be assessed for response by MRI of brain and/or spine after 4 cycles (8 weeks) of treatment according to Response Criteria for Primary CNS Lymphoma. Patients with stable disease or better (CR or PR) will continue treatment for 12 cycles (24 weeks). Complete Response (CR)=no contrast enhancement, normal eye exam. Partial Response (PR)=50 percent decrease in tumor enhancement, minor retinal pigment epithelium abnormality in eye exam. Stable disease (SD)= a change in lesion size that is neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for progressive disease.

  approximately 32 weeks

Secondary Outcomes (2)

• Progression Free Survival (PFS)

  6 and 12 months

• Number of Participants With Serious and Non-serious Adverse Events as a Measure of Safety.

  up to 4 weeks

Study Arms (1)

Rituximab plus Temozolomide

EXPERIMENTAL

Rituximab: 375 mg/m2 IV, days 1, 3, and 5 Temozolomide: 150 mg/m2 PO, days 1-5

Drug: Rituximab plus Temozolomide

Interventions

Rituximab plus Temozolomide DRUG

Treatment cycles will be repeated every 14 days (2 weeks) for the lead-in portion. If no prohibitive toxicities are observed in the first 6 patients during the first 2 treatment cycles, the study will continue enrolling patients. Treatment cycles for the Phase II portion will be repeated every 14 days (2 weeks) for a total of 12 cycles.

Also known as: Rituximab: Rituxin, MabThera, Temozolomide: Temodar

Rituximab plus Temozolomide

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed CD20 positive primary B-cell CNS lymphoma (PCNSL) confirmed by one of the following:
• Brain biopsy or resection;
• Cerebrospinal fluid (CSF) cytology for lymphoma or monoclonal lymphocyte population as defined by cell surface markers.
• No evidence of systemic non-Hodgkin's lymphoma.
• Male or female, and:
• years of age or older, or
• years of age or older and decline methotrexate-based treatment.
• Measurable contrast-enhancing disease by MRI of brain and or spine (with gadolinium contrast).
• ECOG PS equals 2 or less.
• No more than 2 prior chemotherapy regimens.
• Adequate hematologic, renal, and hepatic function.
• Ability to swallow oral medications.
• Female patients who are not of childbearing potential, and female patients of childbearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum pregnancy test within 72 hours prior to start of treatment.
• Male patients willing to use adequate contraceptive measures.
• Life expectancy 8 weeks or greater.

You may not qualify if:

• Previous treatment with rituximab or other monoclonal antibodies, or temozolomide.
• Prior bone marrow or organ transplantation.
• Chemotherapy or investigational drug therapy for cancer up to 21 days prior to day-1 of study.
• T-cell primary CNS lymphoma.
• Known hypersensitivity to dacarbazine (DTIC).
• Active, clinically serious infection greater than CTCAE grade 2. Patients may be eligible upon resolution of the infection.
• Positive test results for chronic hepatitis BsAg infection.
• Chronic treatment with steroids or other immunosuppressive agents for medical conditions other than cancer. Patients who require steroids for treatment of tumor-associated cerebral edema are eligible.
• History of other malignancy up to 5 years prior to study entry which could affect compliance with the protocol or interpretation of results. History of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade, early stage, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with lumpectomy alone with curative intent, are generally eligible.
• History of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York Heart Association Classification III or IV.
• Vaccination with a live-virus vaccine up to 4 weeks prior to onset of study treatment.
• Impairment of gastrointestinal (GI) function or GI disease that, in the opinion of the investigator, may significantly alter the absorption of study drug (e.g., Crohn's disease, ulcerative disease, uncontrolled vomiting, diarrhea, or malabsorption syndrome).
• Significant, concurrent, uncontrolled medical condition which, in the opinion of the investigator, may interfere with patient participation in the study.
• Pregnant or lactating female.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• Genentech, Inc.: collaborator

Study Sites (4)

Yale School of Medicine

New Haven, Connecticut, 06520, United States

Location

Memorial Cancer Institute

Hollywood, Florida, 33021, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

Rituximab; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Two (2) subjects were enrolled in the safety lead-in part of the study. The study closed early due to slow accrual.

Results Point of Contact

• Title: Charles H. Davis, RAC
• Organization: Sarah Cannon Development Innovations

charles.davis2@scri-innovations.com

615-524-4341

Study Officials

• Kent Shih, M.D.

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2014
• First Posted: April 14, 2014
• Study Start: July 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: February 7, 2017
• Results First Posted: February 7, 2017

Record last verified: 2016-12

Locations

US (4)