Methotrexate With or Without Cyclophosphamide in Treating Patients With Lymphocytic Leukemia

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00003910
• Other study ID #: CDR0000067089
• Secondary ID: U10CA021115E5998
• Status: Terminated
• Phase: Phase 2
• Start date: September 15, 1999
• Est. completion date: March 2012

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• 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.

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.

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 information / eligibility

• Status: Terminated
• Enrollment: 59
• Est. completion date: March 2012
• Est. primary completion date: December 1, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia

Intervention

Drug:
• Cyclophosphamide
Patients not responding to MTX after 4 months received Cy orally at 100 mg daily in step two with the same prednisone schedule. In patients showing a partial response, but not a CR, the maximum period of therapy was 1 year.
• Methotrexate
Initial treatment consisted of MTX given orally at 10 mg/m2 in divided doses once weekly.
• Prednisone
Prednisone was given orally at 1 mg/kg per day for 30 days and then tapered off in the subsequent 24 days.

Locations

Country	Name	City	State
United States	McFarland Clinic, PC	Ames	Iowa
United States	Aurora Presbyterian Hospital	Aurora	Colorado
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Boulder Community Hospital	Boulder	Colorado
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	CCOP - Colorado Cancer Research Program	Denver	Colorado
United States	Porter Adventist Hospital	Denver	Colorado
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	Rose Medical Center	Denver	Colorado
United States	St. Anthony Central Hospital	Denver	Colorado
United States	St. Joseph Hospital	Denver	Colorado
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Swedish Medical Center	Englewood	Colorado
United States	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center	Grand Junction	Colorado
United States	North Colorado Medical Center	Greeley	Colorado
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Hutchinson Area Health Care	Hutchinson	Minnesota
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin
United States	Central Pennsylvania Hematology and Medical Oncology Associates, PC	Lemoyne	Pennsylvania
United States	Lewistown Hospital	Lewistown	Pennsylvania
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	St. Rita's Medical Center	Lima	Ohio
United States	Meeker County Memorial Hospital	Litchfield	Minnesota
United States	Sky Ridge Medical Center	Lone Tree	Colorado
United States	Hope Cancer Care Center at Longmont United Hospital	Longmont	Colorado
United States	McKee Medical Center	Loveland	Colorado
United States	Medical Center of Central Georgia	Macon	Georgia
United States	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota
United States	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota
United States	Fox Chase Cancer Center - Philadelphia	Philadelphia	Pennsylvania
United States	St. Mary - Corwin Regional Medical Center	Pueblo	Colorado
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Cancer Center	Saint Louis Park	Minnesota
United States	HealthEast Cancer Care at St. Joseph's Hospital	Saint Paul	Minnesota
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota
United States	Mercy Medical Center - Sioux City	Sioux City	Iowa
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	St. Luke's Regional Medical Center	Sioux City	Iowa
United States	Mount Nittany Medical Center	State College	Pennsylvania
United States	North Suburban Medical Center	Thornton	Colorado
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	HealthEast Cancer Care at Woodwinds Health Campus	Woodbury	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients With Complete or Partial Response to Treatment With MTX	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.	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.
Secondary	Proportion of Patients With Complete or Partial Response to Treatment of CY Among Patients Failing to Respond to MTX	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.	Assessed during the first 4 months of treatment and followed until reaching full study stop date