A Phase II Study of Initial Treatment With Methotrexate in Large Granular Lymphocytic (LGL) Leukemia
18 Years
N/A
Both
Leukemia
Trial Information
A Phase II Study of Initial Treatment With Methotrexate in Large Granular Lymphocytic (LGL) Leukemia
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.
Inclusion Criteria
Inclusion:
- Phenotypic studies from peripheral blood showing CD3+, CD57+ cells greater than
400/mm3 or CD8+ cells greater than 650/mm3 within eight weeks prior to registration
- Evidence for clonal T-cell receptor gene rearrangement within one year prior to
registration
- At least one of the following: Severe neutropenia less than 500/mm3, neutropenia
associated with recurrent infections, symptomatic anemia, or transfusion-dependent
anemia
- Bilirubin ≤ 2.0 mg/dl, SGOT(AST) ≤ 1.5 times normal, and Creatinine ≤ 2.0 mg/dl
within 4 weeks prior to registration
- ECOG performance status of 0-2
- At least 18 years of age
- Written informed consent
Exclusion:
- Prior therapy with oral MTX or oral Cy
- Previous or concurrent malignancies except inactive non-melanoma skin cancer, in situ
carcinoma of the cervix, or other cancer if the patient has been disease free for
over 5 years
- Pregnant or breast-feeding for female patients
- Serious medical illness, other than that treated by the study, which would limit
survival to less than 2 years, or psychiatric condition which would prevent informed
consent
Note: to be eligible for step 2 of this study, patients were required to have no response
after at least 4 months of methotrexate treatment.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete, Partial, and Overall Response Rates of Treatment With MTX, and Also With CY for Patients Failing to Respond to MTX
Outcome Description:
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% impr
Outcome Time Frame:
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.
Safety Issue:
No
Principal Investigator
Thomas P. Loughran, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Milton S. Hershey Medical Center
Authority:
United States: Federal Government
Study ID:
CDR0000067089
NCT ID:
NCT00003910
Start Date:
July 1999
Completion Date:
March 2012
Related Keywords:
- Leukemia
- stage I chronic lymphocytic leukemia
- stage II chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- T-cell large granular lymphocyte leukemia
- LGL clone
- Leukemia
- Leukemia, Lymphoid
Name | Location |
|---|---|
| CCOP - Carle Cancer Center | Urbana, Illinois 61801 |
| CCOP - Metro-Minnesota | Saint Louis Park, Minnesota 55416 |
| Aurora Presbyterian Hospital | Aurora, Colorado 80012 |
| Boulder Community Hospital | Boulder, Colorado 80301-9019 |
| Penrose Cancer Center at Penrose Hospital | Colorado Springs, Colorado 80933 |
| CCOP - Colorado Cancer Research Program | Denver, Colorado 80224-2522 |
| Porter Adventist Hospital | Denver, Colorado 80210 |
| Presbyterian - St. Luke's Medical Center | Denver, Colorado 80218 |
| St. Joseph Hospital | Denver, Colorado 80218 |
| Rose Medical Center | Denver, Colorado 80220 |
| Swedish Medical Center | Englewood, Colorado 80110 |
| St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center | Grand Junction, Colorado 81502 |
| Sky Ridge Medical Center | Lone Tree, Colorado 80124 |
| Hope Cancer Care Center at Longmont United Hospital | Longmont, Colorado 80502 |
| St. Mary - Corwin Regional Medical Center | Pueblo, Colorado 81004 |
| North Suburban Medical Center | Thornton, Colorado 80229 |
| Rush-Copley Cancer Care Center | Aurora, Illinois 60507 |
| Evanston Northwestern Healthcare - Evanston Hospital | Evanston, Illinois 60201-1781 |
| Joliet Oncology-Hematology Associates, Limited - West | Joliet, Illinois 60435 |
| Carle Cancer Center at Carle Foundation Hospital | Urbana, Illinois 61801 |
| Methodist Cancer Center at Methodist Hospital | Indianapolis, Indiana 46202 |
| Saint Anthony Memorial Health Centers | Michigan City, Indiana 46360 |
| Mercy Medical Center - Sioux City | Sioux City, Iowa 51104 |
| Siouxland Hematology-Oncology Associates, LLP | Sioux City, Iowa 51101 |
| St. Luke's Regional Medical Center | Sioux City, Iowa 51104 |
| Bronson Methodist Hospital | Kalamazoo, Michigan 49007 |
| West Michigan Cancer Center | Kalamazoo, Michigan 49007-3731 |
| Borgess Medical Center | Kalamazooaa, Michigan 49001 |
| Fairview Ridges Hospital | Burnsville, Minnesota 55337 |
| Mercy and Unity Cancer Center at Mercy Hospital | Coon Rapids, Minnesota 55433 |
| Fairview Southdale Hospital | Edina, Minnesota 55435 |
| Mercy and Unity Cancer Center at Unity Hospital | Fridley, Minnesota 55432 |
| Hutchinson Area Health Care | Hutchinson, Minnesota 55350 |
| Meeker County Memorial Hospital | Lichfield, Minnesota 55355 |
| Minnesota Oncology Hematology, PA - Maplewood | Maplewood, Minnesota 55109 |
| HealthEast Cancer Care at St. John's Hospital | Maplewood, Minnesota 55109 |
| Hennepin County Medical Center - Minneapolis | Minneapolis, Minnesota 55415 |
| Virginia Piper Cancer Institute at Abbott - Northwestern Hospital | Minneapolis, Minnesota 55407 |
| Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center | Robbinsdale, Minnesota 55422-2900 |
| St. Francis Cancer Center at St. Francis Medical Center | Shakopee, Minnesota 55379 |
| HealthEast Cancer Care at St. Joseph's Hospital | St Paul, Minnesota 55102 |
| Park Nicollet Cancer Center | St. Louis Park, Minnesota 55416 |
| Regions Hospital Cancer Care Center | St. Paul, Minnesota 55101 |
| United Hospital | St. Paul, Minnesota 55102 |
| Ridgeview Medical Center | Waconia, Minnesota 55387 |
| Minnesota Oncology Hematology, PA - Woodbury | Woodbury, Minnesota 55125 |
| HealthEast Cancer Care at Woodwinds Health Campus | Woodbury, Minnesota 55125 |
| Aultman Cancer Center at Aultman Hospital | Canton, Ohio 44710-1799 |
| St. Rita's Medical Center | Lima, Ohio 45801 |
| Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
| Medical College of Wisconsin Cancer Center | Milwaukee, Wisconsin 53226 |
| Froedtert Hospital and Medical College of Wisconsin | Milwaukee, Wisconsin 53226-3596 |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
| Medical Center of Central Georgia | Macon, Georgia 31201 |
| Lewistown Hospital | Lewistown, Pennsylvania 17044 |
| Mount Nittany Medical Center | State College, Pennsylvania 16803 |
| North Colorado Medical Center | Greeley, Colorado 80631 |
| McKee Medical Center | Loveland, Colorado 80539 |
| Gundersen Lutheran Center for Cancer and Blood | La Crosse, Wisconsin 54601 |
| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago, Illinois 60611 |
| Fox Chase Cancer Center - Philadelphia | Philadelphia, Pennsylvania 19111-2497 |
| North Shore Oncology and Hematology Associates, Limited - Libertyville | Libertyville, Illinois 60048 |
| St. Anthony Central Hospital | Denver, Colorado 80204-1335 |
| Exempla Lutheran Medical Center | Wheat Ridge, Colorado 80033 |
| Mercy Cancer Center at Mercy Medical Center - North Iowa | Mason City, Iowa 50401 |
| McFarland Clinic, PC | Ames, Iowa 50010 |
| McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center | Reading, Pennsylvania 19612-6052 |
| Central Pennsylvania Hematology and Medical Oncology Associates, PC | Lemoyne, Pennsylvania 17043 |
