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

Primary Central Nervous System Lymphoma Clinical Trial

Official title:

Phase II Study of High-Dose Rituximab Combined With Temozolomide as Treatment for Patients With Primary CNS Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02113007
• Other study ID #: SCRI CNS 20
• Status: Terminated
• Phase: Phase 2
• First received: April 10, 2014
• Last updated: February 22, 2016
• Start date: July 2014
• Est. completion date: February 2016

Study information

• Verified date: February 2016
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

This is a Phase II, multi-centered, single-arm study. A brief patient lead-in portion will be included to assess safety and feasibility. The first six patients enrolled will be monitored weekly for safety during two treatment cycles (4 weeks) for adverse events to assure there are no unexpected or prohibitive toxicities. If safety signals emerge from this group of patients, the protocol may be discontinued or modified.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. No evidence of systemic non-Hodgkin's lymphoma.

3. Male or female, and:

• 60 years of age or older, or

• 18 years of age or older and decline methotrexate-based treatment.

4. Measurable contrast-enhancing disease by MRI of brain and or spine (with gadolinium contrast).

5. ECOG PS equals 2 or less.

6. No more than 2 prior chemotherapy regimens.

7. Adequate hematologic, renal, and hepatic function.

8. Ability to swallow oral medications.

9. 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.

10. Male patients willing to use adequate contraceptive measures.

11. Life expectancy 8 weeks or greater.

12. HIV negative.

13. Archival tumor block (or 20 unstained slides) for biomarker testing. Patients without archived tumor block material will be allowed to participate in the study.

14. Willingness and ability to comply with study and followup procedures.

15. Ability to understand the nature of this study and give written informed consent.

16. Bone marrow biopsy must be negative for lymphoma.

Exclusion Criteria:

1. Previous treatment with rituximab or other monoclonal antibodies, or temozolomide.

2. Prior bone marrow or organ transplantation.

3. Chemotherapy or investigational drug therapy for cancer up to 21 days prior to day-1 of study.

4. T-cell primary CNS lymphoma.

5. Known hypersensitivity to dacarbazine (DTIC).

6. Active, clinically serious infection greater than CTCAE grade 2. Patients may be eligible upon resolution of the infection.

7. Positive test results for chronic hepatitis BsAg infection.

8. 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.

9. 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.

10. History of unstable or newly diagnosed angina pectoris, recent myocardial infarction (within 6 months of enrollment), New York Heart Association Classification III or IV.

11. Vaccination with a live-virus vaccine up to 4 weeks prior to onset of study treatment.

12. 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).

13. Significant, concurrent, uncontrolled medical condition which, in the opinion of the investigator, may interfere with patient participation in the study.

14. Pregnant or lactating female.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Primary Central Nervous System Lymphoma

Intervention

Drug:
• Rituximab plus Temozolomide
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.

Locations

Country	Name	City	State
United States	Memorial Cancer Institute	Hollywood	Florida
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Florida Hospital Cancer Institute	Orlando	Florida

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	Determine the overall response rate (ORR) of patients with primary central nervous system lymphoma (PCNSL) when treated with high-dose rituximab combined with temozolomide.	up to 36 weeks	Yes
Secondary	Progression Free Survival (PFS)	Six and twelve-month CNS progression-free survival rate.	6 and 12 months	No
Secondary	Number of Participants with Serious and Non-serious Adverse Events	Evaluate toxicity of the high-dose rituximab/temozolomide combination.	up to 4 weeks	Yes