Combination Chemotherapy With or Without Autologous Stem Cell Transplant in Treating Patients With Central Nervous System B-Cell Lymphoma
Conditions
Lymphoma
Conditions: official terms
Lymphoma - Lymphoma, B-Cell
Conditions: Keywords
primary central nervous system non-Hodgkin lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage I adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: carmustine Type: Drug
Name: cytarabine Type: Drug
Name: etoposide Type: Drug
Name: thiotepa Type: Drug
Name: autologous hematopoietic stem cell transplantation Type: Procedure
Name: peripheral blood stem cell transplantation Type: Procedure
Overall Status
Recruiting
Summary
RATIONALE: Giving chemotherapy before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

PURPOSE: This randomized phase II trial studies how well combination chemotherapy given together with autologous stem cell transplant works compared to combination chemotherapy alone in treating patients with central nervous system B-cell lymphoma.
Detailed Description
OBJECTIVES:

Primary

- To compare the two-year progression-free survival (PFS) of patients treated with the myeloablative consolidation treatment strategy of high-dose therapy (HDT)/autologous stem cell transplant (ASCT) versus those treated with non-myeloablative consolidation chemotherapy with cytarabine and etoposide.

Secondary

- To compare the two-year event-free survival (EFS) of patients treated with consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine.

- To compare the overall survival (OS) of patients treated with the consolidation HDT/ASCT versus those treated with consolidation chemotherapy consisting of etoposide and cytarabine.

- To assess the toxicities associated with consolidation HDT/ASCT versus consolidation consisting of etoposide and cytarabine.

- To determine diffusion magnetic resonance imaging (MRI) metrics (ADC_mini, ADC_25%, and ADC_mean) prior to induction chemotherapy, after one full induction chemotherapy cycle, and at the end of induction chemotherapy as a predictor of response and outcome (CALGB 581101 Companion Study).

- To determine brain fludeoxyglucose F 18 (FDG)-positron emission tomography (PET) metrics (tumor SUV and tumor versus background SUV) prior to induction chemotherapy, after one full induction chemotherapy cycle, and at the end of induction chemotherapy as a predictor of response and outcome (CALGB 581101 Companion Study).

- To determine whether low baseline ADC measurements are associated with shorter PFS and OS (CALGB 581101 Companion Study).

- To determine whether reduction in tumor SUV by > 25% on brain FDGPET/ CT after one cycle of induction therapy is associated with improved PFS and OS (CALGB 581101 Companion Study).

- To determine which immunohistochemistry (IHC)-based biomarkers are predictive of an adverse prognosis (CALGB 151113 Companion Study).

- To determine which IHC-based biomarkers are predictive of a favorable prognosis (CALGB 151113) for BCL6 (B-cell CLL/lymphoma 6), and STAT 6 (signal transducer and activator of transcription 6, interleukin-4 induced). (Exploratory)

- To analyze tumor tissue for gene expression profiles, and to correlate these profiles with treatment outcomes (CALGB 151113 Companion Study). (Exploratory)

- To determine whether cerebrospinal fluid (CSF) proteome is a predictor of outcomes (prognostic marker) irrespective of treatment arm (CALGB 151113) for (IL-10 [interleukin-10] and C3 [complement component 3]). (Exploratory)

- To assess at the neurocognitive function of patients treated with consolidation HDT/ASCT versus those treated with consolidation chemotherapy (etoposide and cytarabine) as measured by serial administration of the International Primary Central Nervous System Lymphoma (PCNSL) Collaborative Group (IPCG) neurocognitive battery at and evaluate the long-term survivorship differences between the two arms (CALGB 71105 Companion Study).

- To assess the quality of life of patients treated with consolidation HDT/ASCT versus those treated with consolidation etoposide and cytarabine as measured by the EORTC Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTC-QLQ30/BCM20), and to evaluate the long-term survivorship differences between the two arms (CALGB 71105 Companion Study).

OUTLINE: This is a multicenter study. Patients are stratified according to age and Karnofsky performance status (KPS) (age < 51 years vs age ≥ 51 years and KPS ≥ 70% vs age ≥ 51 years and KPS < 70%).

Induction Chemotherapy: Patients receive methotrexate IV over 4 hours on days 1 and 15 (courses 1-4); leucovorin calcium IV every 6 hours beginning 24 hours after each methotrexate dose (courses 1-4); rituximab IV on days 3, 10, 17, and 24 (course 1), and days 3 and 10 (course 2); temozolomide orally (PO) on days 7-11 (courses 1-4); and cytarabine IV over 2 hours twice daily (BID) on days 1 and 2 (course 5 only). Treatment repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity.

Patients achieving a complete response, complete response unconfirmed, partial response, or stable disease proceed to consolidation therapy.

Consolidation therapy: Patients are randomized to 1 of 2 treatment arms.

- Arm I : Between 3-5 weeks after induction therapy patients undergo stem cell mobilization per participating institution guidelines.

- Consolidation therapy: Beginning 2-4 weeks after stem cell mobilization, patients receive high-dose therapy comprising carmustine IV over 2 hours on day -6 and thiotepa IV over 2 hours on days -5 to -4. Beginning on day 4, patients also receive filgrastim subcutaneously (SC) once a day and continuing until absolute neutrophil count recovers.

- Stem cell rescue: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.

- Arm II: Beginning at least 8 weeks and no later than 16 weeks after day 1 of induction course 5, patients receive cytarabine IV over 2 hours on days 1-4, and etoposide IV continuously over 96 hours on days 1-4. Beginning on day 14, patients also receive filgrastim SC once a day and continuing until absolute neutrophil count recovers.

Tumor tissue, cerebrospinal fluid, and vitreous fluid samples may be collected for banking and correlative studies.

Patients may complete quality-of-life questionnaires at baseline and periodically during study.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 70 Years
Minimum Age: 18 Years
Gender: Both
Criteria: DISEASE CHARACTERISTICS:

- Diagnosis of primary central nervous system (CNS) diffuse large B-cell lymphoma confirmed by one of the following:

- Brain biopsy or resection

- Cerebrospinal fluid

- Vitreous fluid

- No evidence or history of non-Hodgkin lymphoma (NHL) outside of CNS

- No isolated ocular lymphoma or isolated leptomeningeal lymphoma

- At least one measurable, contrast-enhancing brain lesion (≥ 1 cm in length)

PATIENT CHARACTERISTICS:

- Karnofsky performance status ≥ 30% (≥ 50% for patients ages 60-70 years)

- Adequate cardiac function (left ventricular ejection fraction [LVEF] ≥ 50%) and pulmonary function (corrected diffusion capacity of carbon monoxide [DLCO] ≥ 60% predicted)

- Pregnant or nursing patients may not be enrolled; women of childbearing potential must have a negative serum or urine pregnancy test 10-14 days prior to registration; in addition, women and men of childbearing potential must commit to use an effective form of contraception throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom)

- Negative human immunodeficiency virus (HIV) serology

- Negative hepatitis B virus (HBV) and hepatitis C virus (HCV) serology (unless HBV antibody [HBsAb]-positive patient has recently received HBV vaccine, in this case HBcAb should be negative)

- Absolute neutrophil count (ANC) ≥ 1500/mcL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2 times upper limit of normal (ULN)

- Total bilirubin ≤ 3 mg/dL

- Creatinine clearance ≥ 50 mL/min

- Platelet count ≥ 100,000/mcL

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy or radiation therapy for lymphoma

- No history of organ transplantation or ongoing immunosuppressant therapy

- No concurrent palliative radiotherapy
Locations
Dana-Farber/Brigham and Women's Cancer Center
Boston, Massachusetts, United States
Status: Recruiting
Contact: Clinical Trials Office - 617-724-5200
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Status: Recruiting
Contact: Tracy Batchelor, MD, MPH - 617-643-1938
Massachusetts General Hospital
Boston, Massachusetts, United States
Status: Recruiting
Contact: Clinical Trials Office - Massachusetts General Hospital - 877-726-5130
Borgess Medical Center
Kalamazoo, Michigan, United States
Status: Recruiting
Contact: Raymond S. Lord, MD - 269-373-7458
Bronson Methodist Hospital
Kalamazoo, Michigan, United States
Status: Recruiting
Contact: Raymond S. Lord, MD - 269-373-7458
West Michigan Cancer Center
Kalamazoo, Michigan, United States
Status: Recruiting
Contact: Clinical Trials Office - West Michigan Cancer Center - 269-373-7458
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States
Status: Recruiting
Contact: Nina D. Wagner-Johnston - 314-747-7222
SUNY Upstate Medical University Hospital
Syracuse, New York, United States
Status: Recruiting
Contact: Clinical Trials Office - SUNY Upstate Medical University Hospi - 315-464-5476
Natalie Warren Bryant Cancer Center at St. Francis Hospital
Tulsa, Oklahoma, United States
Status: Recruiting
Contact: Joseph P. Lynch, MD - 918-494-8275
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States
Status: Recruiting
Contact: Clinical Trials Office - UPMC Cancer Centers - 412-647-8073
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States
Status: Recruiting
Contact: Clinical Trials Office -Virginia Commonwealth University Masse - 804-628-1939
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
Status: Recruiting
Contact: Maciej M. Mrugala - 206-667-4692
Seattle Cancer Care Alliance
Seattle, Washington, United States
Status: Recruiting
Contact: Clinical Trials Office - Seattle Cancer Care Alliance - 800-804-8824
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States
Status: Recruiting
Contact: Maciej M. Mrugala - 206-598-4100
Start Date
September 2012
Sponsors
Cancer and Leukemia Group B
Source
National Cancer Institute (NCI)
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page