Alemtuzumab Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Lymphocytic Leukemia

NCT ID: NCT00006390

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-07-05

Brief Summary

RATIONALE: Monoclonal antibodies such as alemtuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy. Combining monoclonal antibody therapy, chemotherapy, radiation therapy, and peripheral stem cell transplantation may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of alemtuzumab plus peripheral stem cell transplantation in treating patients who have chronic lymphocytic leukemia.

Detailed Description

OBJECTIVES:

• Determine the ability of in vivo purging with alemtuzumab (monoclonal antibody CD52; Campath-1H) to produce a stem cell graft without detectable leukemia cells in patients with chronic lymphocytic leukemia.
• Determine the ability to successfully mobilize stem cells after in vivo purging with monoclonal antibody CD52 in these patients.
• Determine the toxicity of this treatment regimen in these patients.
• Determine the response to this treatment regimen in these patients at 6 months after peripheral blood stem cell transplantation.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising alemtuzumab (monoclonal antibody CD52; Campath-1H) IV over 2 hours three times a week for 4 weeks.

Beginning no more than 2 weeks after induction therapy, patients receive mobilization chemotherapy comprising cyclophosphamide IV over 1-2 hours on day 1 and filgrastim (G-CSF) subcutaneously (SC) starting on day 2 and continuing until the last day of apheresis. Patients undergo peripheral blood stem cell apheresis on days 10-14.

Beginning 2-4 weeks after apheresis, patients receive a preparative regimen comprising cyclophosphamide IV over 2 hours on days -5 and -4 and fractionated total body irradiation twice a day over 6-10 hours on days -3 to -1. Patients undergo peripheral blood stem cell transplantation on day 0. Patients receive G-CSF SC beginning on day 1 and continuing until blood counts recover.

Patients are followed at 60 days, 1 year, and then annually thereafter until disease progression.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Conditions

Leukemia

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

alemtuzumab

Intervention Type: BIOLOGICAL

filgrastim

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic lymphocytic leukemia (CLL) that meets the following criteria at any point prior to study entry:

• Peripheral blood absolute blood count greater than 5,000/mm^3
• Lymphocytosis must comprise small to moderate size lymphocytes with no more than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically
• Phenotypically characterized B-cell CLL
• Splenomegaly, hepatomegaly, or lymphadenopathy not required for CLL diagnosis
• Must have bone marrow biopsy within 4 weeks of study entry showing cellularity of at least 25% of intratrabecular space and lymphocytes accounting for no more than 30% of nucleated cells

PATIENT CHARACTERISTICS:

Age:

• 18 to 65

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics
• Absolute neutrophil count at least 1,000/mm^3
• Hemoglobin at least 11 g/dL
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 mg/dL (unless secondary to tumor)
• AST or ALT less than 3 times upper limit of normal
• Hepatitis B surface antigen negative
• Hepatitis C RNA negative

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• Left ventricular ejection fraction at least 45% by echocardiogram or MUGA

Pulmonary:

• DLCO, FEV_1, and FVC greater than 50% of predicted

Other:

• No active infection requiring oral or IV antibiotics
• No other prior malignancy within the past two years except basal cell skin cancer or carcinoma in situ of the cervix
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior monoclonal antibody CD52 allowed if at least partial remission was achieved with last treatment

Chemotherapy:

• No more than 2 prior chemotherapy regimens
• At least 3 weeks since prior chemotherapy
• No more than 8 courses of prior fludarabine therapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Eastern Cooperative Oncology Group

Principal Investigators

Ian W. Flinn, MD, PhD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, United States

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Cancer Center at Tufts - New England Medical Center

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

CCOP - Geisinger Clinic and Medical Center

Danville, Pennsylvania, United States

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Abramson Cancer Center at the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Hillman Cancer Center at University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

CCOP - Marshfield Clinic Research Foundation

Marshfield, Wisconsin, United States

Countries

United States

Other Identifiers

ECOG-8998

Identifier Type: -

Identifier Source: secondary_id

CDR0000068272

Identifier Type: -

Identifier Source: org_study_id