Clinical trial NCT00328198: Subcutaneous Alemtuzumab (CAMPATH®, MabCampath®) in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia
Official title: A Phase II Trial to Evaluate the Efficacy and Safety of Subcutaneously Administered Alemtuzumab (CAMPATH®, MabCampath®) in Patients With Previously Treated B-Cell Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: B-Cell Chronic Lymphocytic Leukemia (B-CLL)
Keywords: CAMPATH
Alemtuzumab
Leukemia
MabCampath
Chronic
Subcutaneous
CLL
C-CLL
Relapsed
Refractory
Chronic Lymphocytic Leukemia
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
First posted: 2006-05-19
Enrollment: 86
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 II, open-label, prospective, multicenter study to evaluate the efficacy and safety of subcutaneously administered alemtuzumab (CAMPATH, MabCampath) as therapy for patients with relapsed or refractory B-CLL who have been previously treated.


Eligibility criteria: Inclusion Criteria:

* A diagnosis of B-cell chronic lymphocytic leukemia (B-CLL); according to the National Cancer Institute Working Group (NCI WG) Criteria.
* World Health Organization (WHO) performance status of 0, 1, or 2.
* Life expectancy ≥ 12 weeks.
* Previous therapy with at least one but no more than 5 regimens (single agent or combination regimen). One therapy regimen is defined as consecutive, contiguous cycles of the same drug(s) with no treatment interruptions lasting \> 3 months.
* Patient requires treatment for CLL per the following criteria: -Rai stage III or IV; -Rai stage 0-II with at least one of the following - evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia; Massive (i.e. greater than 6 cm below the left costal margin) or progressive splenomegaly; Progressive lymphocytosis with an increase of greater than 50% over a 2-month period or an anticipated doubling time of less than 6 months; Lymphocyte count \> 100\*10\^9/L; B symptoms.
* More than 3 weeks since prior chemotherapy. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
* More than 3 weeks since using investigational agents. Patient must have recovered from the acute side effects incurred as a result of previous therapy.
* Serum creatinine and conjugated (direct) bilirubin less than or equal to 2 times the institutional upper limit of normal (ULN) unless secondary to direct infiltration of the liver with CLL.
* Female patients with childbearing potential must have a negative pregnancy test (serum or urine) within 2 weeks of first dose of study drug(s). All patients must agree to use an effective contraceptive method while on study treatment, if appropriate, and for a minimum of 6 months following study therapy.
* Signed, written informed consent (in the US, includes The Health Insurance Portability and Accountability Act of 1996 (HIPAA) authorization)

Exclusion Criteria:

* Positive Coombs test and evidence of active hemolysis.
* Platelet count less than 50\*10\^9/L without splenomegaly.
* History of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanized monoclonal antibodies.
* Previously treated with CAMPATH.
* Previous bone marrow transplant.
* Known central nervous system (CNS) involvement with B-CLL
* Active infection, including human immunodeficiency virus (HIV) positive.
* Active second malignancy.
* Recent documented history (within 2 years) of active tuberculosis (TB), current active TB infection, currently receiving anti-tuberculous medication (e.g., INH, rifampin, streptomycin, pyrazinamide, or others).
* Active hepatitis or a history of prior viral hepatitis B or hepatitis C, or positive hepatitis B serologies. Patients with a positive hepatitis B surface antibody (HBsAb) test with a documented history of prior hepatitis B immunization are eligible as long as other criteria are met (i.e. negative tests for: hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) and hepatitis C virus antibody (HCVAb)).
* Other severe, concurrent diseases (e.g., cardiac or pulmonary disease), mental disorders, or major organ malfunction (liver, kidney) that could interfere with the patient ability to participate in the study.
* Pregnant or nursing women.
* Cytomegalovirus (CMV) positive by polymerase chain reaction (PCR) (above the level of detection). A patient that is PCR positive will require treatment to reduce the viral load to a non-detectable level; but such a patient may be considered for study entry once the infection has been treated.
* Medical condition requiring chronic use of oral corticosteroids at a dose higher than physiologic replacement.

Primary outcomes:
measure: Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP)
timeFrame: up to 44 weeks
measure: Percentage of Participants Who Had an Overall Response (OR) as Determined by the Independent Response Review Panel (IRRP)
timeFrame: up to 44 weeks
Secondary outcomes:
measure: Kaplan-Meier Estimates of Progression Free Survival as Determined by the Independent Response Review Panel (IRRP)
timeFrame: up to 5 years
measure: Kaplan-Meier Estimates of Duration of Response as Determined by the Independent Response Review Panel (IRRP)
timeFrame: up to 5 years
measure: Kaplan-Meier Estimates of Overall Survival
timeFrame: up to 5 years
measure: Participants With a Minimal Residual Disease (MRD) Status of Negative
timeFrame: 44 weeks
measure: Participants With Treatment-Emergent Adverse Events (TEAE)
timeFrame: up to 18 weeks of treatment plus 45 days
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores Cancer Center
state: California
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at University of Colorado Health Sciences Center
state: Colorado
city: Colorado Springs
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Tupelo
country: United States
facility: North Mississippi Hematology & Oncology Associates, Ltd.
state: Mississippi
city: Columbus
country: United States
facility: Mid Ohio Oncology Hematology, Inc.
state: Ohio
city: Lubbock
country: United States
facility: Joe Arrington Cancer Center
state: Texas
city: Brussels
country: Belgium
facility: Academisch Ziekenhuis der Vrije Universiteit Brussel
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Brno
country: Czech Republic
facility: University Hospital Brno
city: Hradec Kralove
country: Czech Republic
facility: University Hospital Hradec Kralove (UH HK)
city: Clermont-Ferrand
country: France
facility: Hopital Hotel-Dieu
city: Lille
country: France
facility: Hopital Claude Huriez
city: Nantes
country: France
facility: Hopital Hotel-Dieu, CHU de Nantes-Service d'Hematologie Clinique
city: Belgrade
country: Serbia
facility: Institute of Hematology, Clinical Centre of Serbia
city: Novi Sad
country: Serbia
facility: Clinic of Hematology, Clinical Centre Vojvodina Novi Sad
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Liverpool
country: United Kingdom
facility: Royal Liverpool and Broadgreen Hospitals
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References: