A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL

Official Title: “A Phase II Trial of Alemtuzumab (Campath-1H) and Rituximab (Rituxan) in Patients With Previously Untreated CLL”

RATIONALE: Monoclonal antibodies, such as alemtuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving alemtuzumab together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving alemtuzumab together with rituximab and to see how well it works in treating patients with previously untreated B-cell chronic lymphocytic leukemia.

OBJECTIVES: - To determine the response rate in patients with previously untreated B-cell chronic lymphocytic leukemia treated with alemtuzumab and rituximab. - To evaluate the toxicity of alemtuzumab and rituximab in these patients.

OUTLINE: Patients receive alemtuzumab subcutaneously on days 1, 3, and 5 in weeks 1-18 and rituximab IV on day 1 in weeks 3, 5, 7, 9, 11, 13, 15, and 17 in the absence of disease progression or unacceptable toxicity.

Peripheral blood and bone marrow samples are collected periodically for laboratory biomarker studies. Samples are analyzed for surface markers (e.g., CD3, CD4, CD8, CD10, CD19, CD20, CD25, CD38, CD52, Zap-70) and IgVH by PCR, flow cytometry, and FISH. Samples are also analyzed for alemtuzumab and anti-alemtuzumab antibody levels by flow cytometry.

After completion of study treatment, patients are followed periodically for 5 years.

Intervention(s) in this Clinical Trial

• Biological: Alemtuzumab
  • Alemtuzumab administered subcutaneously 30mg per day, 3 days per week for 18 weeks
• Biological: Rituximab
  • Rituximab administered intravenously at 375mg/m2 every 2 weeks for 18 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Alemtuzumab and Rituximab
  • Administration of Alemtuzumab combined with Rituximab to test the feasibility of combining these two monoclonal antibodies as a first line therapy in patients with B-cell chronic lymphocytic leukemia.

Primary Measures

• To determine the response rate to the study medications, Alemtuzumab and Rituximab
  • Time Frame: At 9 weeks (during therapy), 18 weeks (at the completion of therapy), and 30 weeks
    Safety Issue?: No
• Collect data on the toxicity of the study medications, Alemtuzumab and Rituximab
  • Time Frame: Every 2 weeks while on treatment and then monthly for 6 months, then every 3 months for 4.5 years (54 months)
    Safety Issue?: Yes

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL)*, as defined by the following criteria:
• Peripheral blood absolute lymphocyte count > 5,000/mm³
• Small- to moderate-size lymphocytes with < 55% prolymphocytes, atypical lymphocytes, or lymphoblasts
• Phenotypically characterized B-CLL expressing CD20 and CD52, as defined by the following:
• Predominant population of cells share B-cell antigens with CD-5 in the absence of other pan-T-cell markers (e.g., CD-3, CD-2)
• B-cell expresses either lambda or kappa light chains
• Surface immunoglobulin with low-cell surface density expression NOTE:
• *Presence of splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL
• Requires therapy, as indicated by ≥ 1 of the following criteria:
• Unintentional weight loss > 10% within the past 6 months
• Extreme fatigue (i.e., ECOG performance status 2)
• Fevers > 100.5°F for 2 weeks without evidence of infection
• Night sweats without evidence of infection
• Evidence of progressive marrow failure as manifested by the development of or worsening of anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelet count < 100,000/mm³)
• Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly
• Massive nodes/clusters (> 5 cm), progressive symptomatic adenopathy, or adenopathy resulting in end-organ damage
• Progressive lymphocytosis with an increase of > 50% over 2 months or an anticipated doubling time < 6 months
• Marked hypogammaglobulinemia or the development of a monoclonal protein in the absence of any of the above criteria for active disease is not sufficient for eligibility

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• ANC ≥ 1,000/mm³*
• Platelet count ≥ 50,000/mm³*
• Hemoglobin ≥ 10 g/dL*
• Serum creatinine ≤ 2.0 mg/dL OR creatinine clearance > 40 mL/min
• Bilirubin < 2 mg/dL
• AST and ALT ≤ 2 times normal (unless secondary to tumor infiltration/lymphadenopathy)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after completion of study treatment
• No active autoimmune anemia or thrombocytopenia
• No active infection requiring oral or intravenous antibiotics
• No second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless curatively treated ≥ 2 years ago NOTE: *If cytopenias are due to degree of bone marrow involvement, patient may be eligible at the discretion of the principal investigator.

PRIOR CONCURRENT THERAPY:

• Prior corticosteroid therapy allowed
• No prior cytotoxic therapy (other than corticosteroids)

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: Northwestern University Other

Overall Clinical Trial Officials and Contacts

Olga Frankfurt, MD Principal Investigator Northwestern University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00858117

Study ID Number: NU 04H6

ClinicalTrials.gov Identifier: NCT00858117

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database