Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma or Acute Lymphocytic Leukemia

Lymphoma Clinical Trial

Official title:

A Pilot Study of Dose Intensification of Methotrexate in Patients With Advanced-Stage (III/IV) Small Non-Cleaved Cell Non-Hodgkins Lymphoma and B-Cell All

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005977
• Other study ID #: 9917
• Secondary ID: COG-9917CDR00000
• Status: Completed
• Phase: Phase 3
• First received: July 5, 2000
• Last updated: August 19, 2013
• Start date: September 2000
• Est. completion date: September 2006

Study information

• Verified date: August 2013
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating patients who have non-Hodgkin's lymphoma or acute lymphocytic leukemia.

Description:

OBJECTIVES:

• Determine if increasing the methotrexate dose in combination with standard treatment is feasible in patients with advanced small noncleaved cell non-Hodgkin's lymphoma or B-cell acute lymphocytic leukemia.

• Assess the toxicity of this intensified therapy in these patients.

• Assess the feasibility of treating these patients that have CNS disease at diagnosis with this intensified therapy plus etoposide and ifosfamide.

• Assess toxicities and late effects of this intensive therapy on the central nervous system, cardiac function, and fertility in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to stage and disease (stage III non-Hodgkin's lymphoma (NHL) vs stage IV NHL with no CNS involvement vs stage IV NHL with CNS involvement vs B-cell acute lymphocytic leukemia (B-ALL) with no CNS involvement vs B-ALL with CNS involvement).

Patients receive methotrexate and cytarabine intrathecally on days 1, 4, 11, and 36 (on day 40 for patients with stage IV NHL or B-ALL only) in combination with alternating courses of: A) cyclophosphamide IV every 12 hours for a total of six doses on days 1-3, doxorubicin IV over 30 minutes on day 4, vincristine IV on days 4 and 11, dexamethasone IV or orally twice daily on days 1-5, and filgrastim (G-CSF) subcutaneously (SQ) or IV over 30 minutes beginning on day 5 and continuing until blood counts recover and B) methotrexate IV over 24 hours on day 18, methotrexate intrathecally on day 18, dexamethasone IV or orally twice daily on days 18-22, leucovorin calcium IV or orally every 6 hours for a total of 6 doses on days 20-21, cytarabine IV over 48 hours on days 20-21, and G-CSF SQ or IV over 30 minutes beginning on day 22 and continuing until blood counts recover. Patients with stage III NHL receive at total of 5 courses of treatment (A-B-A-B-A) and patients with stage IV NHL or B-ALL with no CNS involvement receive a total of 6 courses of treatment (A-B-A-B-A-B).

Patients with CNS involvement receive a third course of treatment: C) etoposide IV over 1 hour on days 36-40, ifosfamide IV over 1 hour on days 36-40, oral dexamethasone twice daily on days 36-40, and G-CSF SQ or IV over 30 minutes beginning on day 41 and continuing until blood counts recover. Patients with CNS involvement receive a total of 7 courses of treatment (A-B-C-A-B-A-B).

Patients are followed every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 27-80 patients will be accrued for this study over 24 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: September 2006
• Est. primary completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 22 Years

Eligibility

DISEASE CHARACTERISTICS:

• One of the following diagnoses:

• Histologically confirmed small noncleaved cell non-Hodgkin's lymphoma

• Stage III or IV

• Burkitt's or non-Burkitt's by the Working Formulation OR

• Burkitt's or Burkitt's-like by the REAL classification

• Histologically confirmed B-cell acute lymphocytic leukemia

• At least 25% blasts in bone marrow

• FAB L3 morphology

• FAB L1 morphology allowed if blasts show B-cell markers (CD19, 20, 22) and surface immunoglobulin positivity

• Must be registered on POG-9900 in past 8 days

PATIENT CHARACTERISTICS:

Age:

• Under 22 at time of diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant or nursing

• Negative pregnancy test

• HIV positive allowed

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• No concurrent use of dexamethasone as antiemetic

Radiotherapy:

• Not specified

Surgery:

• Prior surgery allowed

Other:

• No prior therapy except surgery

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• filgrastim
Given IV

Drug:
• cyclophosphamide
Given IV
• cytarabine
Given IV
• dexamethasone
Given IV
• doxorubicin hydrochloride
Given IV
• etoposide
Given IV
• ifosfamide
Given IV
• leucovorin calcium
Given IV
• methotrexate
Given IV
• vincristine sulfate
Given IV

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Children's Hospital	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier de L'Universite Laval	Sainte Foy	Quebec
Canada	Laval University Medical Center	Sainte-Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Puerto Rico	San Jorge Childrens Hospital	Santurce
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Clinique de Pediatrie	Geneva
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
United States	University of New Mexico School of Medicine	Albuquerque	New Mexico
United States	Mission Saint Joseph's Health System	Asheville	North Carolina
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Boston Floating Hospital Infants and Children	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Medical School-Charleston	Charleston	West Virginia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Healthcare	Charlotte	North Carolina
United States	Cancer Center at the University of Virginia	Charlottesville	Virginia
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Missouri-Columbia Hospital and Clinics	Columbia	Missouri
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Texas Oncology P.A.	Dallas	Texas
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	St. John Hospital and Medical Center	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Hurley Medical Center	Flint	Michigan
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Shands Hospital and Clinics, University of Florida	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Children's Hospital of Greenville Hospital System	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	James H. Quillen College of Medicine	Johnson City	Tennessee
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	University of California San Diego Cancer Center	La Jolla	California
United States	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Baptist Hospital of Miami	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	University of Miami-Jackson Memorial Hospital Medical Center	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	University of South Alabama Medical Center	Mobile	Alabama
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Yale Comprehensive Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Mount Sinai School of Medicine	New York	New York
United States	Hope Children's Hospital	Oak Lawn	Illinois
United States	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma
United States	Florida Hospital Cancer Institute	Orlando	Florida
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Maine Children's Cancer Program	Portland	Maine
United States	Naval Medical Center, Portsmouth	Portsmouth	Virginia
United States	Massey Cancer Center	Richmond	Virginia
United States	Carilion Roanoke Community Hospital	Roanoke	Virginia
United States	University of Rochester Cancer Center	Rochester	New York
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	MBCCOP - South Texas Pediatric	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Children's Hospital and Health Center	San Diego	California
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	All Children's Hospital	St. Petersburg	Florida
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	CCOP - Florida Pediatric	Tampa	Florida
United States	Scott and White Clinic	Temple	Texas
United States	Arizona Cancer Center	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center	Tulsa	Oklahoma
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	St. Mary's Hospital	West Palm Beach	Florida
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Netherlands,  Puerto Rico,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival	Assess the effect of high dose methotrexate in combination with standard treatment per the POG 9317 protocol on 1-year event-free survival (EFS), monitor and assess toxicity, and estimate the hospitalization costs for the treatment of toxicity related side effects.	1 year	Yes