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

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01511562

Collaborator

National Cancer Institute (NCI) (NIH)

113

Enrollment

126

Locations

Arms

0.9

Patients Per Site

Study Details

Study Description

Brief Summary

The purpose of this study is to find out what effects (good and/or bad) treatment with chemotherapy and stem cell transplant compared with chemotherapy alone will have on primary CNS B-cell lymphoma. Currently the best treatment for patients with primary CNS B-cell lymphoma is not known.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: carmustine Drug: cytarabine Drug: etoposide Drug: thiotepa Procedure: stem cell transplant Drug: G-CSF	Phase 2

Detailed Description

Primary Objective:

To compare the two-year progression-free survival (PFS) of patients treated with the myeloablative consolidation treatment strategy of HDT/ASCT versus those treated with non-myeloablative consolidation chemotherapy with cytarabine and etoposide

Secondary Objectives:

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 MRI metrics (ADCmini, ADC25%, and ADCmean) 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)
To determine brain FDG-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)
To determine whether low baseline ADC measurements are associated with shorter PFS and OS (CALGB 581101)
To determine whether reduction in tumor SUV by > 25% on brain FDG-PET/CT after one cycle of induction therapy is associated with improved PFS and OS (CALGB 581101)
To determine which IHC-based biomarkers are predictive of an adverse prognosis (CALGB

To determine which IHC-based biomarkers are predictive of a favorable prognosis (CALGB

for BCL6 (B-cell CLL/lymphoma 6), and STAT 6 (signal transducer and activator of transcription 6, interleukin-4 induced)

To analyze tumor tissue for gene expression profiles, and to correlate these profiles with treatment outcomes (CALGB 151113)
To determine whether 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)
To assess 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 PCNSL Collaborative Group (IPCG) neurocognitive battery and evaluate the long-term survivorship differences between the two arms (CALGB 71105)

Study Design

Study Type:

Interventional

Actual Enrollment :

113 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase II Trial of Myeloablative Versus Non-Myeloablative Consolidation Chemotherapy for Newly Diagnosed Primary CNS B-cell Lymphoma

Study Start Date :

Sep 1, 2012

Anticipated Primary Completion Date :

Oct 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Other: Arm I Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant.	Drug: carmustine Given IV Drug: thiotepa Given IV Procedure: stem cell transplant Drug: G-CSF
Other: Arm II Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo consolidation chemotherapy.	Drug: cytarabine Given IV Drug: etoposide Given IV Drug: G-CSF

Arm

Intervention/Treatment

Other: Arm I

Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo stem cell transplant.

Drug: carmustine

Given IV

Drug: thiotepa

Given IV

Procedure: stem cell transplant

Drug: G-CSF

Other: Arm II

Patients undergo induction therapy for five cycles as defined in the protocol. Patients undergo consolidation chemotherapy.

Drug: cytarabine

Given IV

Drug: etoposide

Given IV

Drug: G-CSF

Outcome Measures

Primary Outcome Measures

progression free survival [Up to 10 years]

Secondary Outcome Measures

event free survival [Up to 10 years]
number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Up to 10 years]
overall survival [Up to 10 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Documentation of Disease: Diagnosis of primary CNS diffuse large B-cell lymphoma confirmed by one of the following: brain biopsy or resection, cerebrospinal fluid and vitreous fluid.
Other Lymphomas: Patients must have no evidence or history of non-Hodgkin lymphoma (NHL) outside of CNS.
Previous Treatment: Patients must have no prior chemotherapy or radiation therapy for lymphoma.
Age- Patients must be between the ages of 18 and 75 years.
Karnofsky Performance Scale - Patients must measure Karnofsky Performance Scale ≥ 30 (≥ 50 for patients ages 60-70).
Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing; 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; appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom)
HIV - Patients must have negative HIV serology.
Hepatitis - Patients must have negative HCV serology (unless HBsAb positive patient has recently received HBV vaccine, in this case HBcAb should be negative). All patients must be screened for hepatitis B infection before starting treatment. Those patients who test positive for hepatitis B should be closely monitored for evidence of active HBV infection and hepatitis during and for several months after rituximab treatment. PCNSL patients with a history of hepatitis B infection should be treated with entecavir or lamivudine (physician discretion for choice of drug) as antiviral prophylaxis to prevent hepatitis B reactivation.
Organ Transplant or Immunosuppressant Therapy - Patient must have no history of organ transplantation or ongoing immunosuppressant therapy.
Required Initial Laboratory Values: ANC ≥ 1500/mcL, AST and ALT < 2 x upper limit of normal (ULN), total bilirubin ≤ 3 mg/dL, creatinine clearance ≥ 50 mL/min, platelet count ≥ 100,000/mcL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anchorage Associates in Radiation Medicine	Anchorage	Alaska	United States	98508
2	Anchorage Radiation Therapy Center	Anchorage	Alaska	United States	99504
3	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
4	Alaska Oncology and Hematology LLC	Anchorage	Alaska	United States	99508
5	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
6	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
7	Katmai Oncology Group	Anchorage	Alaska	United States	99508
8	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
9	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
10	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
11	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
12	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
13	UCSF Medical Center-Parnassus	San Francisco	California	United States	94143
14	Yale University	New Haven	Connecticut	United States	06520
15	Moffitt Cancer Center	Tampa	Florida	United States	33612
16	Emory University/Winship Cancer Institute	Atlanta	Georgia	United States	30322
17	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
18	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho	United States	83619
19	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho	United States	83642
20	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho	United States	83686
21	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho	United States	83301
22	University of Illinois	Chicago	Illinois	United States	60612
23	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
24	Reid Health	Richmond	Indiana	United States	47374
25	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
26	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky	United States	41017
27	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
28	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
29	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
30	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
31	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
32	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
33	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
34	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
35	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
36	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
37	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
38	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
39	Lakeland Community Hospital	Niles	Michigan	United States	49120
40	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
41	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
42	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
43	Munson Medical Center	Traverse City	Michigan	United States	49684
44	Metro Health Hospital	Wyoming	Michigan	United States	49519
45	Mayo Clinic	Rochester	Minnesota	United States	55905
46	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
47	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
48	Weill Medical College of Cornell University	New York	New York	United States	10065
49	University of Rochester	Rochester	New York	United States	14642
50	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
51	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
52	Duke University Medical Center	Durham	North Carolina	United States	27710
53	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio	United States	45459
54	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio	United States	45202
55	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio	United States	45211
56	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio	United States	45230
57	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
58	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio	United States	45242
59	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
60	Miami Valley Hospital	Dayton	Ohio	United States	45409
61	Dayton Physicians LLC-Samaritan North	Dayton	Ohio	United States	45415
62	Samaritan North Health Center	Dayton	Ohio	United States	45415
63	Dayton NCI Community Oncology Research Program	Dayton	Ohio	United States	45420
64	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio	United States	45014
65	Armes Family Cancer Center	Findlay	Ohio	United States	45840
66	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
67	Orion Cancer Care	Findlay	Ohio	United States	45840
68	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
69	Dayton Physicians LLC-Atrium	Franklin	Ohio	United States	45005
70	Dayton Physicians LLC-Wayne	Greenville	Ohio	United States	45331
71	Wayne Hospital	Greenville	Ohio	United States	45331
72	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
73	Kettering Medical Center	Kettering	Ohio	United States	45429
74	Dayton Physicians LLC-Signal Point	Middletown	Ohio	United States	45042
75	Dayton Physicians LLC-Wilson	Sidney	Ohio	United States	45365
76	Springfield Regional Cancer Center	Springfield	Ohio	United States	45504
77	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
78	Dayton Physicians LLC-Upper Valley	Troy	Ohio	United States	45373
79	Upper Valley Medical Center	Troy	Ohio	United States	45373
80	Surgical Associates Inc	Tulsa	Oklahoma	United States	74136
81	Warren Clinic Oncology-Tulsa	Tulsa	Oklahoma	United States	74146
82	Saint Charles Health System	Bend	Oregon	United States	97701
83	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
84	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon	United States	97015
85	Bay Area Hospital	Coos Bay	Oregon	United States	97420
86	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
87	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
88	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
89	Providence Portland Medical Center	Portland	Oregon	United States	97213
90	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
91	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
92	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
93	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania	United States	15232
94	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
95	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
96	University of Vermont Medical Center	Burlington	Vermont	United States	05401
97	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
98	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
99	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	United States	98520
100	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
101	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington	United States	98005
102	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
103	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
104	Swedish Medical Center-Edmonds	Edmonds	Washington	United States	98026
105	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
106	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
107	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
108	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
109	Minor and James Medical PLLC	Seattle	Washington	United States	98104
110	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
111	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
112	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
113	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
114	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
115	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
116	University of Washington Medical Center	Seattle	Washington	United States	98195
117	Providence Regional Cancer System-Shelton	Shelton	Washington	United States	98584
118	Rockwood Clinic Cancer Treatment Center-Valley	Spokane Valley	Washington	United States	99216
119	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington	United States	99204
120	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
121	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
122	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
123	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
124	Providence Regional Cancer System-Yelm	Yelm	Washington	United States	98597
125	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin	United States	54601
126	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792