Methotrexate With or Without Cyclophosphamide in Treating Patients With Lymphocytic Leukemia
- Conditions
- Leukemia
- Interventions
- Registration Number
- NCT00003910
- Lead Sponsor
- Eastern Cooperative Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase II trial to study the effectiveness of methotrexate with or without cyclophosphamide in treating patients who have lymphocytic leukemia with neutropenia or anemia.
- Detailed Description
LGL leukemia is characterized by clonal expansion of cytotoxic T cells. Prominent clinical features include neutropenia, anemia, and rheumatoid arthritis. The terminal effector memory phenotype (CD3+/CD8+/CD57+/CD45RA+/CD62L-) of leukemic LGL suggest a pivotal chronic antigen driven immune response. LGL survival is then promoted by PDGF and IL-15, resulting in global dysregulation of apoptosis and resistance to normal pathways of activation-induced death. These pathogenic features explain why treatment of LGL leukemia is based on immunosuppression therapy. However, no standard therapy has been established due to the absence of large prospective trials.
Oral low dose MTX has been shown to be efficacious in the treatment of neutropenia. However, response to MTX is slow, requiring several months for the neutrophil count to increase above 500/mm3. Also, complete clinical remission may not be achieved until after one year of MTX therapy. Oral Cy has been the primary drug used for the treatment of severe transfusion-dependent anemia. Beneficial clinical effects are seen despite this treatment having no apparent effect on the abnormal LGL clone. Normal hematocrits are maintained after cessation of Cy and these results contrast the effects seen with MTX, in which clinical remissions are often associated with the disappearance of the clone.
This phase II trial undertaken by the Eastern Cooperative Group (ECOG) was initiated to investigate the mechanism of treatment response in patients with LGL leukemia, who need treatment for anemia or neutropenia.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 59
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Methotrexate (Cy if no response to MTX) Methotrexate MTX given orally at 10 mg/m2 in divided doses once weekly. Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days. Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule. Methotrexate (Cy if no response to MTX) Cyclophosphamide MTX given orally at 10 mg/m2 in divided doses once weekly. Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days. Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule. Methotrexate (Cy if no response to MTX) Prednisone MTX given orally at 10 mg/m2 in divided doses once weekly. Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days. Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule.
- Primary Outcome Measures
Name Time Method Proportion of Patients With Complete or Partial Response to Treatment With MTX Assessed during the first 4 months, then at least every three months for two years. Then every six months until five years after study entry, and every 12 months thereafter until full study stop date. We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count \> 1500/mm3, lymphocyte count\< 4000/mm3, hemoglobin \> 11 g/dl, and platelet count \> 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% improvement.
- Secondary Outcome Measures
Name Time Method Proportion of Patients With Complete or Partial Response to Treatment of CY Among Patients Failing to Respond to MTX Assessed during the first 4 months of treatment and followed until reaching full study stop date We will report the overall response rate below. Complete remission requires that all of the following be present for at least four weeks: The patient must have a normal CBC including neutrophil count \> 1500/mm3, lymphocyte count\< 4000/mm3, hemoglobin \> 11 g/dl, and platelet count \> 100,000/mm3. In addition, the patient must have a normal LGL count. A complete response will be attained if CD8+ cells were less than 760/mm³. A partial response will be defined as achievement of any one of the following in the absence of CR. The response must last for at least four weeks:In patients being treated for severe neutropenia (less than 500 neutrophils/mm3) an improvement to over 500 neutrophils/mm3 will be considered a partial response, as long as that improvement represents at least a 50% improvement.
Trial Locations
- Locations (68)
Minnesota Oncology Hematology, PA - Woodbury
🇺🇸Woodbury, Minnesota, United States
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
🇺🇸Chicago, Illinois, United States
McFarland Clinic, PC
🇺🇸Ames, Iowa, United States
McKee Medical Center
🇺🇸Loveland, Colorado, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
HealthEast Cancer Care at St. John's Hospital
🇺🇸Maplewood, Minnesota, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
HealthEast Cancer Care at St. Joseph's Hospital
🇺🇸Saint Paul, Minnesota, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
HealthEast Cancer Care at Woodwinds Health Campus
🇺🇸Woodbury, Minnesota, United States
Minnesota Oncology Hematology, PA - Maplewood
🇺🇸Maplewood, Minnesota, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Presbyterian - St. Luke's Medical Center
🇺🇸Denver, Colorado, United States
CCOP - Colorado Cancer Research Program
🇺🇸Denver, Colorado, United States
St. Anthony Central Hospital
🇺🇸Denver, Colorado, United States
St. Joseph Hospital
🇺🇸Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸Denver, Colorado, United States
Methodist Cancer Center at Methodist Hospital
🇺🇸Indianapolis, Indiana, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Hennepin County Medical Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Penrose Cancer Center at Penrose Hospital
🇺🇸Colorado Springs, Colorado, United States
Sky Ridge Medical Center
🇺🇸Lone Tree, Colorado, United States
Hope Cancer Care Center at Longmont United Hospital
🇺🇸Longmont, Colorado, United States
St. Mary - Corwin Regional Medical Center
🇺🇸Pueblo, Colorado, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
🇺🇸Grand Junction, Colorado, United States
North Suburban Medical Center
🇺🇸Thornton, Colorado, United States
Evanston Northwestern Healthcare - Evanston Hospital
🇺🇸Evanston, Illinois, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
St. Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Meeker County Memorial Hospital
🇺🇸Litchfield, Minnesota, United States
Regions Hospital Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Aurora Presbyterian Hospital
🇺🇸Aurora, Colorado, United States
Boulder Community Hospital
🇺🇸Boulder, Colorado, United States
Rose Medical Center
🇺🇸Denver, Colorado, United States
North Colorado Medical Center
🇺🇸Greeley, Colorado, United States
Exempla Lutheran Medical Center
🇺🇸Wheat Ridge, Colorado, United States
Rush-Copley Cancer Care Center
🇺🇸Aurora, Illinois, United States
Medical Center of Central Georgia
🇺🇸Macon, Georgia, United States
Joliet Oncology-Hematology Associates, Limited - West
🇺🇸Joliet, Illinois, United States
CCOP - Carle Cancer Center
🇺🇸Urbana, Illinois, United States
North Shore Oncology and Hematology Associates, Limited - Libertyville
🇺🇸Libertyville, Illinois, United States
Saint Anthony Memorial Health Centers
🇺🇸Michigan City, Indiana, United States
Carle Cancer Center at Carle Foundation Hospital
🇺🇸Urbana, Illinois, United States
Mercy Medical Center - Sioux City
🇺🇸Sioux City, Iowa, United States
Mercy Cancer Center at Mercy Medical Center - North Iowa
🇺🇸Mason City, Iowa, United States
Borgess Medical Center
🇺🇸Kalamazoo, Michigan, United States
Bronson Methodist Hospital
🇺🇸Kalamazoo, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
Aultman Cancer Center at Aultman Hospital
🇺🇸Canton, Ohio, United States
St. Rita's Medical Center
🇺🇸Lima, Ohio, United States
Fox Chase Cancer Center - Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Central Pennsylvania Hematology and Medical Oncology Associates, PC
🇺🇸Lemoyne, Pennsylvania, United States
Lewistown Hospital
🇺🇸Lewistown, Pennsylvania, United States
Gundersen Lutheran Center for Cancer and Blood
🇺🇸La Crosse, Wisconsin, United States
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
🇺🇸Reading, Pennsylvania, United States
Froedtert Hospital and Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Mount Nittany Medical Center
🇺🇸State College, Pennsylvania, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States