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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00436904
First received: February 15, 2007
Last updated: November 21, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Leukemia
Drug: Alemtuzumab
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Antibody Therapy With Alemtuzumab and Rituximab for Initial Treatment of High Risk Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Confirmed Response, Defined as Objective Complete Remission or Partial Remission for a Duration of at Least 2 Months [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    Confirmed response is defined as a > 50% decrease in clinical symptoms from baseline and recovery from blood counts.

  • Number of Participants With Treatment Related Adverse Events [ Time Frame: Weekly for first 6 weeks, then monthly for 6 months, then at 9 and 12 months post registration ] [ Designated as safety issue: Yes ]

    Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. Grade refers to the severity of the AE.

    >

    > Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE, Grade 5: Death related AE



Secondary Outcome Measures:
  • Time to Response [ Time Frame: Registration to first response (up to 5 years) ] [ Designated as safety issue: No ]
    Calculated from the date of registration until the first date at which the patient's objective status was classified as a response. In patients who do not achieve a response, time to response will be censored at the patient's last evaluation date. Response is defined the same way as in the response primary outcome measure.

  • Duration of Response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Duration of response is calculated from the date of documented response until the date of progression in the subset of patients who respond to treatment. In patients who have not yet progressed, duration of response will be censored at the patient's last evaluation date.

  • Survival [ Time Frame: Death or last follow-up (up to 5 years) ] [ Designated as safety issue: No ]
    Survival is calculated from the date of registration to the date of death due to any cause. In patients who are still alive, survival will be censored at the last date when the patient was known to be alive.

  • Time to Disease Progression [ Time Frame: Time from registration to progression (up to 5 years) ] [ Designated as safety issue: No ]
    Calculated from date of registration to date of disease progression. In patients that have not progressed, time to disease progression will be censored at the patient's last evaluation date.


Enrollment: 30
Study Start Date: December 2004
Study Completion Date: November 2011
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alemtuzumab + Rituximab
Alemtuzumab 30mg Monday, Wednesday, and Friday x 5 weeks, Rituximab 375/mg/m2 IV weekly (Wednesday) x 4 weeks (weeks 2-5)
Drug: Alemtuzumab
30 mg Monday, Wednesday, and Friday x 5 weeks
Drug: Rituximab
375mg/m2 IV weekly (Wednesday) x 4 weeks (weeks 2-5)

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

PRIOR CONCURRENT THERAPY:

  • No prior treatment for CLL
  • Prior corticosteroids allowed
  • No prior radiotherapy
  • More than 4 weeks since prior major surgery
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436904

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Clive S. Zent, MD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00436904     History of Changes
Other Study ID Numbers: CDR0000529809, P30CA015083, MC038G, 801-04, 106.G0309, U3023s
Study First Received: February 15, 2007
Results First Received: September 16, 2011
Last Updated: November 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
stage 0 chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Alemtuzumab
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014