Clinical trial NCT00335140: Rituximab and Combination Chemotherapy in Treating Patients With Primary Central Nervous System Lymphoma
Official title: Phase II Study of Rituximab Given in Conjunction With Standard Chemotherapy in Primary Central Nervous System (CNS) Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoma
Keywords: primary central nervous system non-Hodgkin lymphoma
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
First posted: 2006-06-08
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as methotrexate, leucovorin, vincristine, procarbazine, dexamethasone, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with primary central nervous system (CNS) lymphoma.

Detailed description: OBJECTIVES:

Primary

* Determine the complete response rate.

Secondary

* Determine the progression-free survival of these patients.
* Determine the proportion of progression-free and overall survival in these patients.
* Determine rituximab cerebrospinal fluid pharmacokinetics (only in patients requiring intrathecal chemotherapy).

OUTLINE: This is a multicenter study.

Patients receive rituximab IV 3 times weekly in weeks 1-4; high-dose methotrexate IV over 2 hours in weeks 1, 3, 5, and 9; oral or IV leucovorin calcium every 6 hours for 12 doses beginning 24 hours after the start of methotrexate in weeks 1, 3, 5, and 9; vincristine IV in weeks 1, 3, 5, 7, and 9; oral procarbazine hydrochloride daily on days 1-7 in weeks 1, 5, and 9; oral dexamethasone daily in weeks 1-6; and cytarabine IV over 2 hours twice weekly in weeks 11 and 14.

Patients with positive cerebrospinal fluid also receive methotrexate intrathecally and oral leucovorin calcium every 12 hours for 8 doses beginning 24 hours after the start of methotrexate in weeks 2, 4, 6, 8, and 10.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 43 patients will be accrued for this study.

Eligibility criteria: Inclusion criteria:

* Histologically confirmed non-Hodgkin's lymphoma by brain biopsy
* Patients with inconclusive biopsy or patients who are not candidates for biopsy must have typical CT scan or MRI of the brain AND meet ≥ 1 of the following criteria:

  * Positive cerebrospinal fluid cytology for lymphoma OR a monoclonal lymphoid population as defined by cell surface markers or immunoglobulin gene rearrangement studies
  * Biopsy-proven involvement of the vitreous or uvea if cells are apparent in the posterior chamber or vitreous by ophthalmological examination
* Bideminsionally measurable disease, defined as contrast-enhancing tumor ≥ 1 cm by pretreatment MRI/CT scan

  * Meningeal or vitreous involvement constitutes evaluable but not measurable disease
  * If an excisional, rather than a needle biopsy was done, measurable disease must be present on a postoperative scan (not a PET-CT scan)
* ECOG performance status 0-3
* Absolute granulocyte count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin ≤ upper limit of normal (ULN)
* SGOT ≤ 2.0 times ULN
* Creatinine clearance ≥ 50 mL/min
* Negative pregnancy test
* Fertile patients must use effective contraception

Exclusion criteria:

* Pregnant or nursing
* HIV-1 positivity
* Other malignancy within the past 5 years except basal cell skin cancer or any carcinoma in situ
* Pre-existing immunodeficiency
* Hepatitis B surface antigen positivity
* Systemic lymphoma (as determined by pre-registration CT scans and physical examination)
* Prior chemotherapy or radiotherapy for primary central nervous system lymphoma
* Prior organ or bone marrow transplantation

Primary outcomes:
measure: Complete Response Rate - Locally Reviewed
timeFrame: For the primary endpoint, complete response will be based on disease status at three weeks post the end of therapy (week 17).
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
city: Hinsdale
country: United States
facility: Hinsdale Hematology Oncology Associates
state: Illinois
city: Ames
country: United States
facility: McFarland Clinic, PC
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center - Sioux City
state: Iowa
city: Sioux City
country: United States
facility: St. Luke's Regional Medical Center
state: Iowa
city: Anthony
country: United States
facility: Hospital District Sixth of Harper County
state: Kansas
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Kalamazoo
country: United States
facility: Borgess Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology, PA - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Robbinsdale
country: United States
facility: Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology Hematology, PA - Woodbury
state: Minnesota
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Canton
country: United States
facility: Aultman Cancer Center at Aultman Hospital
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Cancer Care Center at MetroHealth Medical Center
state: Ohio
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Hazleton
country: United States
facility: Geisinger Hazleton Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group - Scenery Park
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Medical X-Ray Center, PC
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Charleston
country: United States
facility: West Virginia University Health Sciences Center - Charleston
state: West Virginia
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Lode J. Swinnen, MD
role: STUDY_CHAIR
affiliation: University of Utah
name: Deborah T. Blumenthal, MD
role: STUDY_CHAIR
References:
citation: Swinnen LJ, O'Neill A, Imus PH, Gujar S, Schiff D, Kleinberg LR, Advani RH, Dunbar EM, Moore D, Grossman SA. Phase II study of rituximab given in conjunction with standard chemotherapy in primary central nervous system lymphoma (PCNSL): a trial of the ECOG-ACRIN cancer research group (E1F05). Oncotarget. 2017 Nov 6;9(1):766-773. doi: 10.18632/oncotarget.22332. eCollection 2018 Jan 2.