Alemtuzumab and Rituximab in Treating Patients With High-Risk, Early-Stage Chronic Lymphocytic Leukemia

Mayo Clinic

Status and phase

Completed

Phase 2

Conditions

Leukemia

Treatments

Drug: Alemtuzumab

Drug: Rituximab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00436904

P30CA015083 (U.S. NIH Grant/Contract)

MC038G (Other Identifier)

106.G0309 (Other Identifier)

801-04 (Other Identifier)

U3023s (Other Identifier)

CDR0000529809

Details and patient eligibility

About

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 and how well giving alemtuzumab together with rituximab works in treating patients with high-risk, early-stage chronic lymphocytic leukemia.

Full description

OBJECTIVES:

Primary

Determine the rate of complete and overall response to alemtuzumab and rituximab in patients with high-risk, early-stage chronic lymphocytic leukemia.
Determine the toxicity of this regimen in these patients. Secondary
Determine the overall survival and time to progression of patients treated with this regimen.
Determine time to response and duration of response in patients treated with this regimen.
Correlate prognostic markers 11q-, 17p-, unmutated VH gene, and CD38+ with clinical outcome.
Determine response to this regimen using an expanded definition of response that includes minimal residual disease detected by sensitive flow cytometry in patients in complete clinical remission and single rearranged IgVH gene detected by polymerase chain reaction in patients with no monoclonal population on flow cytometry.
Correlate in vitro response with clinical outcome in patients treated with this regimen.
Determine if alemtuzumab and rituximab are synergistic in vitro.
Determine the mechanism of action of this regimen in vitro.
Determine the effect of this regimen on immune function.
Monitor T-lymphocyte, natural killer cell, and monocyte number during and after treatment in these patients.
Serially evaluate T-lymphocyte immunophenotype and function in patients treated with this regimen.
Monitor recovery of humoral immunity by serial serum protein electrophoresis, immunofixation electrophoresis, and immunoglobulin quantification.

OUTLINE:

Dose-escalation (week 1): Patients receive rituximab IV on day 1 and escalating doses of alemtuzumab subcutaneously (SC) on days 3-5 in week 1.
Treatment (weeks 2-5): Patients receive alemtuzumab SC on days 1-3 (at the highest dose administered during week 1) and rituximab IV on day 3 in weeks 2-5 in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection at baseline and periodically during study treatment for pharmacokinetic and prognostic biomarker (11q-, 17p-, unmutated IgVH, and CD38 expression by flow cytometry and fluorescent in-situ hybridization) studies. Immune function (CDR3 T-cell receptor by reverse transcriptase-polymerase chain reaction) and in vitro and in vivo response are also examined.

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

PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.

Enrollment

30 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

* Diagnosis of B-cell chronic lymphocytic leukemia (CLL)

Early-stage, biologically high-risk disease defined by the following criteria:

Rai stage 0-II (does not meet standard NCI-sponsored Working Group criteria for treatment)
Clinical and phenotypic features manifested in the peripheral blood, including the following:
- Minimum threshold peripheral blood lymphocyte count of > 5,000/mm³
- Small-to-moderate peripheral blood lymphocytes with ≤ 55% prolymphocytes
- Monoclonality of B lymphocytes by immunophenotypic evaluation, demonstrating co-expression of CD19, CD5, and CD23 antigens, surface expression of CD20 and CD52, and B-cell monoclonal population defined by light-chain exclusions
Poor prognosis demonstrated by ≥ 1 of the following high-risk parameters:
- Unmutated human immunoglobulin variable region heavy chain (IgVH) gene and CD38 expression (≥ 30% cells positive on flow cytometry) OR unmutated IgVH ZAP-70 expression (≥ 20% cells positive on flow cytometry) = 11q- = 17p-

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Creatinine ≤ 1.5 times upper limit of normal (ULN)
Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 times ULN
AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)
Hemoglobin ≥ 9.0 g/dL
No New York Heart Association class III-IV heart disease
No myocardial infarction within the past month
No uncontrolled infection
No active HIV infection
No evidence of autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
No other active primary malignancy requiring treatment or limiting survival to less than 2 years