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”

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.

Intervention(s) in this Clinical Trial

• Biological: Alemtuzumab
  • Campath 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 dose 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.
• Biological: Alemtuzumab
  • Campath 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 Campath (with no escalation period) administered SC (at alternating injection sites) 3 times per week (e.g., Monday, Wednesday, Friday) for up to 18 weeks. Campath 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, Campath may be administered by the patient or care giver if the patient meets conditions specified in the protocol guidelines for home administration.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Dose escalation
  • (3mg, 10mg, 30mg)
• Experimental: No escalation
  • No escalation

Primary Measures

• Best disease response to CAMPATH treatment administered subcutaneously for up to 18 weeks in patients with B-Cell Chronic Lymphocytic Leukemia (B-CLL) who have been previously treated.
  • Time Frame: 44 weeks with additional observation period thereafter
    Safety Issue?: No

Secondary Measures

• Progression free survival (PFS).
  • Time Frame: 44 weeks with additional observation period thereafter
    Safety Issue?: No
• Duration of response.
  • Time Frame: 44 weeks with additional observation period thereafter
    Safety Issue?: No
• Overall survival.
  • Time Frame: 44 weeks with additional observation period thereafter
    Safety Issue?: No
• Minimal residual disease (MRD) status by flow cytometry analysis of bone marrow and peripheral blood.
  • Time Frame: 44 weeks with additional observation period thereafter
    Safety Issue?: No
• Safety of CAMPATH administered subcutaneously.
  • Time Frame: 44 weeks with additional observation period thereafter
    Safety Issue?: Yes

Inclusion Criteria:

• A diagnosis of B-CLL; according to the NCI WG Criteria.
• 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 x 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 x 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 HIPPA authorization)

Exclusion Criteria:

• Positive Coombs test and evidence of active hemolysis.
• Platelet count less than 50 x 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 secondary malignancy.
• Recent documented history (within 2 years) of active tuberculosis (TB), current active TB infection, currently receiving anti-tuberculosis 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.
• CMV positive by 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Genzyme Industry

Overall Clinical Trial Officials and Contacts

Medical Monitor Study Director Genzyme  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00328198

Study ID Number: CAM203

ClinicalTrials.gov Identifier: NCT00328198

Health Authority: United States: Food and Drug Administration