Subcutaneous Alemtuzumab (CAMPATH®, MabCampath®) in Relapsed/Refractory B-Cell Chronic Lymphocytic Leukemia

NCT ID: NCT00328198

Last Updated: 2014-03-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2011-08-31

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.

Conditions

B-Cell Chronic Lymphocytic Leukemia (B-CLL)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose escalation

Alemtuzumab is administered using escalating doses and alternating injection sites. The dose is escalated as tolerated using 3mg, 10mg, and 30mg administered subcutaneously (SC) (if tolerated).

Group Type: EXPERIMENTAL

Alemtuzumab

Intervention Type: BIOLOGICAL

Alemtuzumab is administered using escalating doses and alternating injection sites. The dose is escalated as tolerated using 3mg, 10mg, and 30mg administered subcutaneously (SC) (if tolerated). When escalation to 30 mg is tolerated, all subsequent doses are administered at 30 mg SC 3 times per week at alternating injection sites for up to 18 weeks.

Part 1 of the study: The first 20 patients will be randomized to either Arm 1 (dose escalation) or Arm 2 (no escalation). Part 1 of the study has been completed; no additional patients will be enrolled in Part 1. An assigned review panel has reviewed the safety data from Part 1 and determined that all patients will be enrolled and treated under a no escalation schedule for Part 2 of the study.

No escalation

Alemtuzumab treatment is started immediately at the 30mg dose (with no escalation period), administered subcutaneously at alternating injection sites 3 times per week for up to 18 weeks.

Group Type: EXPERIMENTAL

Alemtuzumab

Intervention Type: BIOLOGICAL

Alemtuzumab treatment is started immediately at the 30mg dose (with no escalation period), administered SC at alternating injection sites 3 times per week for up to 18 weeks.

Part 2 of the study: All patients are currently being enrolled under the no escalation schedule for Part 2 of the study. All patients in Part 2 will be treated with 30mg of alemtuzumab (with no escalation period) administered SC (at alternating injection sites) 3 times per week (e.g., Monday, Wednesday, Friday) for up to 18 weeks. Alemtuzumab is to be administered in a supervised medical setting on an outpatient basis for the first three weeks, after which some study centers may allow a home administration option, with one weekly clinic visit. Under the home administration option, alemtuzumab may be administered by the patient or care giver if the patient meets conditions specified in the protocol guidelines for home administration.

Interventions

Alemtuzumab

Alemtuzumab is administered using escalating doses and alternating injection sites. The dose is escalated as tolerated using 3mg, 10mg, and 30mg administered subcutaneously (SC) (if tolerated). When escalation to 30 mg is tolerated, all subsequent doses are administered at 30 mg SC 3 times per week at alternating injection sites for up to 18 weeks.

Part 1 of the study: The first 20 patients will be randomized to either Arm 1 (dose escalation) or Arm 2 (no escalation). Part 1 of the study has been completed; no additional patients will be enrolled in Part 1. An assigned review panel has reviewed the safety data from Part 1 and determined that all patients will be enrolled and treated under a no escalation schedule for Part 2 of the study.

Intervention Type: BIOLOGICAL

Alemtuzumab

Alemtuzumab treatment is started immediately at the 30mg dose (with no escalation period), administered SC at alternating injection sites 3 times per week for up to 18 weeks.

Part 2 of the study: All patients are currently being enrolled under the no escalation schedule for Part 2 of the study. All patients in Part 2 will be treated with 30mg of alemtuzumab (with no escalation period) administered SC (at alternating injection sites) 3 times per week (e.g., Monday, Wednesday, Friday) for up to 18 weeks. Alemtuzumab is to be administered in a supervised medical setting on an outpatient basis for the first three weeks, after which some study centers may allow a home administration option, with one weekly clinic visit. Under the home administration option, alemtuzumab may be administered by the patient or care giver if the patient meets conditions specified in the protocol guidelines for home administration.

Intervention Type: BIOLOGICAL

Other Intervention Names

Campath®, MabCampath®; Campath®, MabCampath®

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.

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

Sponsors

Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma

INDUSTRY

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Genzyme, a Sanofi Company

Locations

Moores Cancer Center

La Jolla, California, United States

Wilshire Oncology Medical Group

La Verne, California, United States

University of Colorado Cancer Center at University of Colorado Health Sciences Center

Aurora, Colorado, United States

Rocky Mountain Cancer Centers

Colorado Springs, Colorado, United States

North Mississippi Hematology & Oncology Associates, Ltd.

Tupelo, Mississippi, United States

Mid Ohio Oncology Hematology, Inc.

Columbus, Ohio, United States

Joe Arrington Cancer Center

Lubbock, Texas, United States

Academisch Ziekenhuis der Vrije Universiteit Brussel

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Universitair Ziekenhuis Leuven

Leuven, , Belgium

University Hospital Brno

Brno, , Czechia

University Hospital Hradec Kralove (UH HK)

Hradec Králové, , Czechia

Hopital Hotel-Dieu

Clermont-Ferrand, , France

Hopital Claude Huriez

Lille, , France

Hopital Hotel-Dieu, CHU de Nantes-Service d'Hematologie Clinique

Nantes, , France

Institute of Hematology, Clinical Centre of Serbia

Belgrade, , Serbia

Clinic of Hematology, Clinical Centre Vojvodina Novi Sad

Novi Sad, , Serbia

Leeds General Infirmary

Leeds, , United Kingdom

Royal Liverpool and Broadgreen Hospitals

Liverpool, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Countries

United States; Belgium; Czechia; France; Serbia; United Kingdom

Other Identifiers

2005-005074-69

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAM203

Identifier Type: -

Identifier Source: org_study_id