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Combination Chemotherapy With or Without Autologous Stem Cell Transplant in Treating Patients With Central Nervous System B-Cell Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by National Cancer Institute (NCI)
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01511562
First received: January 13, 2012
Last updated: February 2, 2013
Last verified: February 2013

January 13, 2012
February 2, 2013
September 2012
April 2014   (final data collection date for primary outcome measure)
Two-year PFS [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01511562 on ClinicalTrials.gov Archive Site
  • EFS and OS estimated for each arm by Kaplan-Meier method, and compared between the two arms using the log-rank test [ Designated as safety issue: No ]
  • Toxicity rate compared between the arms using Fisher's exact method [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Combination Chemotherapy With or Without Autologous Stem Cell Transplant in Treating Patients With Central Nervous System B-Cell Lymphoma
A Randomized Phase II Trial of Myeloablative Versus Non-Myeloablative Consolidation Chemotherapy for Newly Diagnosed Primary CNS B-cell Lymphoma

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.

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.

Interventional
Phase 2
Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Lymphoma
  • Drug: carmustine
    Given IV
  • Drug: cytarabine
    Given IV
  • Drug: etoposide
    Given IV
  • Drug: thiotepa
    Given IV
  • Procedure: autologous hematopoietic stem cell transplantation
    Undergo autologous HSCT
  • Procedure: peripheral blood stem cell transplantation
    Undergo autologous HSCT
  • Experimental: Arm I
    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) until absolute neutrophil count recovers. Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
    Interventions:
    • Drug: carmustine
    • Drug: thiotepa
    • Procedure: autologous hematopoietic stem cell transplantation
    • Procedure: peripheral blood stem cell transplantation
  • Experimental: 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 until absolute neutrophil count recovers.
    Interventions:
    • Drug: cytarabine
    • Drug: etoposide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
160
Not Provided
April 2014   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
United States
 
NCT01511562
CDR0000721927, CALGB-51101
Not Provided
Monica M. Bertagnolli, Cancer and Leukemia Group B
Cancer and Leukemia Group B
National Cancer Institute (NCI)
Principal Investigator: Tracy Batchelor, MD, MPH Massachusetts General Hospital
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP