Clinical trial NCT00858117: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2009-03-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Patients Treated With Alemtuzumab and Rituximab Combination With a Response (CR or PR) Assessed by NCI-WG 1996 Criteria With Lymph-adenopathy and Organomegaly Measured During Physical Examination
timeFrame: At week 9, and post-18 weeks then every 3 months for a year and up every 6 months for up to 2 years
measure: Number of Patients Treated With Alemtuzumab and Rituximab Combination With Response (CR or PR) Assessed by NCI-WG 1996 Criteria With Measurements of the Lymph Nodes and Spleen Size by CT Scans
timeFrame: At week 9, and post-18 weeks then every 3 months for a year and up every 6 months for up to 2 years
Secondary outcomes:
measure: Toxicity of the Study Medications, Alemtuzumab and Rituximab
timeFrame: During treatment, 18 weeks
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University, Northwestern Medical Faculty Foundation
state: Illinois
Study officials:
affiliation: Northwestern University
name: Olga Frankfurt, MD
role: PRINCIPAL_INVESTIGATOR
References: