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

Brief Summary

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.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
  • Study Primary Completion Date: August 2011

Interventions Used in this Clinical Trial

  • Biological: 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.
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: 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).
  • Experimental: 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.

Outcome Measures for this Clinical Trial

Primary Measures

  • Number of Participants With Best Disease Response as Determined by the Independent Response Review Panel (IRRP)
    • Time Frame: up to 44 weeks
      Safety Issue?: No
  • Percentage of Participants Who Had an Overall Response (OR) as Determined by the Independent Response Review Panel (IRRP)
    • Time Frame: up to 44 weeks
      Safety Issue?: No

Secondary Measures

  • Kaplan-Meier Estimates of Progression Free Survival as Determined by the Independent Response Review Panel (IRRP)
    • Time Frame: up to 5 years
      Safety Issue?: No
  • Kaplan-Meier Estimates of Duration of Response as Determined by the Independent Response Review Panel (IRRP)
    • Time Frame: up to 5 years
      Safety Issue?: No
  • Kaplan-Meier Estimates of Overall Survival
    • Time Frame: up to 5 years
      Safety Issue?: No
  • Participants With a Minimal Residual Disease (MRD) Status of Negative
    • Time Frame: 44 weeks
      Safety Issue?: No
  • Participants With Treatment-Emergent Adverse Events (TEAE)
    • Time Frame: up to 18 weeks of treatment plus 45 days
      Safety Issue?: Yes

Criteria for Participation in this Clinical Trial

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.

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

Clinical Trial Investigator Information

  • Lead Sponsor
    • Genzyme, a Sanofi Company
  • Collaborator
    • Bayer Healthcare Pharmaceuticals, Inc./Bayer Schering Pharma
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Monitor, Study Director, Genzyme, a Sanofi Company

Source

Clinical Trials content is provided directly by the US National Institutes of Health via ClinicalTrials.gov and is not reviewed separately by ClinicalTrialsFeeds.org. Every page of information about a specific clinical trial contains a unique identifier which can be used to find further details directly from the National Institutes of Health.

The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00328198