The Addition of Temozolomide to Conditioning for Autologous Transplantation in Relapsed & Refractory Central Nervous System (CNS) Lymphoma
Conditions
B-Cell Lymphoma Originating in the CNS
Conditions: official terms
Lymphoma - Lymphoma, B-Cell
Conditions: Keywords
Relapsed, Refractory, Primary Central Nervous System B-cell Lymphoma, Autologous Stem Cell Transplant, Temozolomide, B-Cell Lymphoma, RBEAM, Conditioning Regimen
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Temozolomide
Type: Drug
Overall Status
Recruiting
Summary
Currently there is no standard of care for relapsed or refractory primary central nervous system (CNS) lymphoma. After high-dose methotrexate or radiation therapy, the best approach to relapsed disease is undefined. Common practice is the regimen RBEAM as a conditioning regimen in this patient population prior to transplantation. The RBEAM regimen includes R (rituximab), B (BCNU), E (etoposide), A (Ara-C (cytarabine)) and M (melphalan). In addition, dexamethasone is included in the regimen although not noted in the RBEAM mnemonic. However, the melphalan used in this combination is not thought to have much CNS penetration. Therefore, temozolomide, an alkylating agent known to penetrate the CNS and approved by the FDA for brain tumors will be used and evaluated in this study instead of melphalan.

The aim of this study is to determine an effective and safe dose of temozolomide orally administered to patients with relapsed primary CNS lymphoma over the 5 days preceding autologous stem-cell transplantation. The hope is that the conditioning regimen DRBEAT [D (dexamethasone) (R (rituximab), B (BCNU), E (etoposide), A (Ara-C (cytarabine)) and T (temozolomide)] will significantly improve the survival of patients with relapsed CNS lymphoma.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 75 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Patients ≥ 18 years of age and ≤ 75 years of age

2. Patients must have Central Nervous System (CNS) involvement with a mature B-cell non-Hodgkin's Lymphoma, (WHO criteria)

3. Patients must meet one of the below criteria:

- Patients who have achieved a complete response (CR) or partial response (PR) after initial therapy for Central Nervous System (CNS) B-cell lymphoma, OR

- Patients with relapsed or progressed disease following therapy for CNS B-cell lymphoma who has achieved a subsequent CR or PR following salvage chemotherapy, OR

- Patients who are initially refractory to therapy for CNS B-cell lymphoma but who have achieved a CR or PR following a salvage chemotherapy regimen, OR

- Patients who have developed CNS relapse from systemic B-cell Non-Hodgkin's lymphoma, and have evidence of chemotherapy sensitive lymphoma.

4. Patients fit for autologous stem cell transplantation

5. Patients able to understand and willing to sign a written informed consent document

Exclusion Criteria:

1. Patients with primary CNS B-cell lymphoma in remission status post primary, initial therapy

2. Patients initially enrolled at relapse but who were not responsive to induction therapy will not be continued on the study

3. Patients whose life expectancy is severely limited by diseases other than malignancy

4. Karnofsky Performance Score <60

5. Patients who are pregnant or breastfeeding

6. Patients who are HIV seropositive

7. Patients who have an uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month

8. Patients with symptomatic coronary artery disease, uncontrolled congestive heart failure. Left Ventricular Ejection Fraction is not required to be measured, however if it is measured, patient is excluded if ejection fraction is <30%

9. Patients requiring supplementary continuous oxygen.

10. Patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function and histology, and for the degree of portal hypertension. Patients with any of the following liver function abnormalities will be excluded

1. Fulminant liver failure

2. Cirrhosis with evidence of portal hypertension or bridging fibrosis

3. Alcoholic hepatitis

4. Esophageal varices

5. A history of bleeding esophageal varices

6. Hepatic encephalopathy

7. Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time

8. Ascites related to portal hypertension

9. Chronic viral hepatitis with total serum bilirubin >3 mg/dL ____mg/dL

10. Symptomatic biliary disease

11. Patients with non-B-cell lymphomas or brain tumors that are not lymphomas are Excluded from the study. Non-B-cell lymphomas include: any T-cell lymphoma, natural killer (NK)-cell lymphomas, and Hodgkin lymphomas

12. Patients for whom an insufficient number of stem cells (<2 X 106/kg) have been collected
Location
Cedars Sinai Medical Center
Los Angeles, California, United States
Status: Recruiting
Contact: Almar Guevarra, RN - 310-423-1365 - Almar.Guevarra@cshs.org
Start Date
September 2010
Completion Date
December 2018
Sponsors
Cedars-Sinai Medical Center
Source
Cedars-Sinai Medical Center
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page