Clinical trial NCT00006390: Alemtuzumab Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Lymphocytic Leukemia
Official title: Phase II Study of Campath-1H (NSC #950010) and Peripheral Blood Stem Cell Transplant for Patients With Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Lakeside Chicago
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Cancer Center at Tufts - New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Hackensack
country: United States
facility: CCOP - Northern New Jersey
state: New Jersey
city: Danville
country: United States
facility: CCOP - Geisinger Clinic and Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Abramson Cancer Center at the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hillman Cancer Center at University of Pittsburgh Cancer Institute
state: Pennsylvania
city: Madison
country: United States
facility: University of Wisconsin Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: CCOP - Marshfield Clinic Research Foundation
state: Wisconsin
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Ian W. Flinn, MD, PhD
role: STUDY_CHAIR
References: