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A Phase II Study of Initial Treatment With Methotrexate in Large Granular Lymphocytic (LGL) Leukemia


Phase 2
18 Years
N/A
Not Enrolling
Both
Leukemia

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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 CenterUrbana, Illinois  61801
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Aurora Presbyterian HospitalAurora, Colorado  80012
Boulder Community HospitalBoulder, Colorado  80301-9019
Penrose Cancer Center at Penrose HospitalColorado Springs, Colorado  80933
CCOP - Colorado Cancer Research ProgramDenver, Colorado  80224-2522
Porter Adventist HospitalDenver, Colorado  80210
Presbyterian - St. Luke's Medical CenterDenver, Colorado  80218
St. Joseph HospitalDenver, Colorado  80218
Rose Medical CenterDenver, Colorado  80220
Swedish Medical CenterEnglewood, Colorado  80110
St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical CenterGrand Junction, Colorado  81502
Sky Ridge Medical CenterLone Tree, Colorado  80124
Hope Cancer Care Center at Longmont United HospitalLongmont, Colorado  80502
St. Mary - Corwin Regional Medical CenterPueblo, Colorado  81004
North Suburban Medical CenterThornton, Colorado  80229
Rush-Copley Cancer Care CenterAurora, Illinois  60507
Evanston Northwestern Healthcare - Evanston HospitalEvanston, Illinois  60201-1781
Joliet Oncology-Hematology Associates, Limited - WestJoliet, Illinois  60435
Carle Cancer Center at Carle Foundation HospitalUrbana, Illinois  61801
Methodist Cancer Center at Methodist HospitalIndianapolis, Indiana  46202
Saint Anthony Memorial Health CentersMichigan City, Indiana  46360
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
Bronson Methodist HospitalKalamazoo, Michigan  49007
West Michigan Cancer CenterKalamazoo, Michigan  49007-3731
Borgess Medical CenterKalamazooaa, Michigan  49001
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Meeker County Memorial HospitalLichfield, Minnesota  55355
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
HealthEast Cancer Care at St. Joseph's HospitalSt Paul, Minnesota  55102
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
HealthEast Cancer Care at Woodwinds Health CampusWoodbury, Minnesota  55125
Aultman Cancer Center at Aultman HospitalCanton, Ohio  44710-1799
St. Rita's Medical CenterLima, Ohio  45801
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Medical College of Wisconsin Cancer CenterMilwaukee, Wisconsin  53226
Froedtert Hospital and Medical College of WisconsinMilwaukee, Wisconsin  53226-3596
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsBaltimore, Maryland  21231-2410
Medical Center of Central GeorgiaMacon, Georgia  31201
Lewistown HospitalLewistown, Pennsylvania  17044
Mount Nittany Medical CenterState College, Pennsylvania  16803
North Colorado Medical CenterGreeley, Colorado  80631
McKee Medical CenterLoveland, Colorado  80539
Gundersen Lutheran Center for Cancer and BloodLa Crosse, Wisconsin  54601
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Fox Chase Cancer Center - PhiladelphiaPhiladelphia, Pennsylvania  19111-2497
North Shore Oncology and Hematology Associates, Limited - LibertyvilleLibertyville, Illinois  60048
St. Anthony Central HospitalDenver, Colorado  80204-1335
Exempla Lutheran Medical CenterWheat Ridge, Colorado  80033
Mercy Cancer Center at Mercy Medical Center - North IowaMason City, Iowa  50401
McFarland Clinic, PCAmes, Iowa  50010
McGlinn Family Regional Cancer Center at Reading Hospital and Medical CenterReading, Pennsylvania  19612-6052
Central Pennsylvania Hematology and Medical Oncology Associates, PCLemoyne, Pennsylvania  17043