Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Closed 18 and over NCI MAYO-MC038G MAYO-IRB-801-04, NCT00436904

Objectives

Primary

1. Determine the rate of complete and overall response to alemtuzumab and rituximab in patients with high-risk, early-stage chronic lymphocytic leukemia.
2. Determine the toxicity of this regimen in these patients.

Secondary

1. Determine the overall and progression-free survival of patients treated with this regimen.
2. Determine time to response and duration of response in patients treated with this regimen.
3. Correlate prognostic markers 11q-, 17p-, unmutated VH gene, and CD38+ with clinical outcome.
4. 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.
5. Correlate in vitro response with clinical outcome in patients treated with this regimen.
6. Determine if alemtuzumab and rituximab are synergistic in vitro.
7. Determine the mechanism of action of this regimen in vitro.
8. Determine the effect of this regimen on immune function.
9. Monitor T-lymphocyte, natural killer cell, and monocyte number during and after treatment in these patients.
10. Serially evaluate T-lymphocyte immunophenotype and function in patients treated with this regimen.
11. Monitor recovery of humoral immunity by serial serum protein electrophoresis, immunofixation electrophoresis, and immunoglobulin quantification.

Entry 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-

Prior/Concurrent Therapy:

• No prior treatment for CLL
• Prior corticosteroids allowed
• No prior radiotherapy
• More than 4 weeks since prior major surgery

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

Expected Enrollment

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

Outcomes

Confirmed response, defined as objective complete remission or partial remission for a duration of at least 2 months
Toxicity

Time to response
Duration of response
Survival
Time to disease progression

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.

Zent CS, Call TG, Shanafelt TD, et al.: Early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Cancer 113 (8): 2110-8, 2008.[PUBMED Abstract]

Zent CS, Secreto CR, LaPlant BR, et al.: Direct and complement dependent cytotoxicity in CLL cells from patients with high-risk early-intermediate stage chronic lymphocytic leukemia (CLL) treated with alemtuzumab and rituximab. Leuk Res 32 (12): 1849-56, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Clive Zent, MD, Protocol chair		Ph: 507-284-2511
Neil Kay, MD, Protocol co-chair		Ph: 507-284-2511 Email: kay.neil@mayo.edu
Timothy Call, MD, Protocol co-chair		Ph: 507-284-2511
Robert Phyliky, MD, Protocol co-chair		Ph: 507-284-3417

Registry Information
Official Title		Antibody Therapy with Alemtuzumab and Rituximab for Initial Treatment of High Risk Chronic Lymphocytic Leukemia
Trial Start Date		2004-12-17
Trial Completion Date		2008-08-01 (estimated)
Registered in ClinicalTrials.gov		NCT00436904
Date Submitted to PDQ		2006-12-22
Information Last Verified		2009-01-13
NCI Grant/Contract Number		CA15083

Back to Top