Clinical trial NCT00046683: Efficacy/Safety of Frontline Alemtuzumab (Campath, MabCampath) vs Chlorambucil in Patients With Progressive B-Cell Lymphocytic Leukemia
Official title: A Phase III Study to Evaluate the Efficacy and Safety of Front-Line Therapy With Alemtuzumab (Campath, MabCampath) vs Chlorambucil in Patients With Progressive B-Cell Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: B Cell Chronic Lymphocytic Leukemia
Keywords: Adult acute leukemia
Adult chronic leukemia
Childhood leukemia
Campath
Alemtuzumab
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2002-10-02
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase III, open-label, multicenter, randomized, comparative study of Campath versus chlorambucil as front line therapy in patients with progressive B-Cell Lymphocytic Leukemia (B-CLL). Eligible patients must have previously untreated, Rai stage I-IV disease, and be experiencing progression of their B-CLL requiring treatment. Patients who meet all eligibility criteria may be randomized on a 1:1 basis to receive either Campath or chlorambucil. An estimated 284 patients (142 per treatment arm) from approximately 40 or more investigational sites will be randomized to one of the two treatment arms.


Eligibility criteria: Inclusion Criteria:

* Histopathologically confirmed diagnosis of B-CLL with CD5, CD19, or CD23 positive clone.
* Rai Stage I through IV disease with evidence of progression as evidenced by the presence of one or more of the following:1. Disease-related B symptoms (fever of greater than 38 celsius (100.5 F) for greater than or equal to 2 weeks without evidence of infection, night sweats without evidence of infection, weight loss \>10% within previous 6 months. 2. Evidence of progression marrow failure as manifested by: a. decrease in hemoglobin to \<11g/dL or b. decrease in platelet count to \<100x10 to the ninth/L within the previous 6 months or c. decrease in absolute neutrophil count (ANC) to \<1.0x10 to the ninth/L within the previous 6 months. 3. Progressive splenomegaly to \>2 cm below the left costal margin or other organomegaly with progressive increase over 2 consecutive clinic visits greater than or equal to 2 weeks apart. 4. Progressive lymphadenopathy with at least 5 sites of involvement with either two nodes at least 2cm in longest diameter or one node greater than or equal to 5cm in longest diameter with progressive increase over 2 consecutive visits greater than or equal to weeks apart. 5. Progressive lymphocytes with an increase of \>50% over a 2-month period, or an anticipated doubling time of less than 6 months.
* Received no previous chemotherapy for B-CLL.
* Life expectancy of at least 12 weeks.
* WHO performance status of 0, 1, or 2.
* Serum creatinine less or equal to 2.0 times the institutional upper limit of normal (ULN) value.
* Adequate liver function as indicated by a total bilirubin, AST, and ALT less or equal to 2 times the institutional ULN value, unless directly attributable to the disease.
* Female patients with childbearing potential must have a negative serum pregnancy test within 2 weeks prior to randomization. Male and female patients must agree to use an effective contraceptive method while on study treatment, if appropriate, and for a minimum of 6 months after study therapy.
* Signed, written informed consent.
* 18 years of age or older.

Exclusion Criteria:

* ANC less than 500 million per liter or platelet count less than 10 billion per liter.
* Medical condition requiring chronic use of oral corticosteroids.
* Autoimmune thrombocytopenia.
* Previous bone marrow transplant.
* Use of investigational agents within previous 30 days.
* Positive for HIV.
* Past history of anaphylaxis following exposure to rat or mouse-derived complementary determining region (CDR) grafted humanized monoclonal antibodies.
* Active infection.
* Serious cardiac or pulmonary disease that could interfere with their ability to participate in the study.
* Recent documented (with in 2 years) of active tuberculosis (TB), current active TB, or currently receiving anti-tuberculosis medication.
* Active secondary malignancy.
* Central nervous system involvement with CLL.
* Positive quantitative CMV by PCR assay (using the laboratory normal ranges).
* A diagnosis of mantle cell lymphoma.
* Other severe, concurrent diseases or mental disorders.
* Pregnant or lactating women.

Primary outcomes:
measure: Campath vs. chlorambucil
Secondary outcomes:
measure: survival comparison
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: Little Rock
country: United States
state: Arkansas
city: Ft. Myers
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Hines
country: United States
state: Illinois
city: Louisville
country: United States
state: Kentucky
city: Paducah
country: United States
state: Kentucky
city: Lafayette
country: United States
state: Louisiana
city: Jackson
country: United States
state: Mississippi
city: Tupelo
country: United States
state: Mississippi
city: Jefferson City
country: United States
state: Missouri
city: Kansas City
country: United States
state: Missouri
city: Billings
country: United States
state: Montana
city: Omaha
country: United States
state: Nebraska
city: New Hyde Park
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: San Antonio
country: United States
state: Texas
city: Norfolk
country: United States
state: Virginia
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: