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LeukemiaPhase 2NCT00436904

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

A Phase 2 study testing Alemtuzumab and Rituximab in people with Leukemia, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Leukemia
What is being tested?
Alemtuzumab and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
Dec 2004to Nov 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Antibody Therapy With Alemtuzumab and Rituximab for Initial Treatment of High Risk Chronic Lymphocytic Leukemia

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.

Read the 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.

Conditions
Leukemia
Being tested
Alemtuzumab, Rituximab
Keywords
stage 0 chronic lymphocytic leukemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, B-cell chronic lymphocytic leukemia
Medical subject headings
Leukemia, Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlemtuzumabDrug

    30 mg Monday, Wednesday, and Friday x 5 weeks

  • RituximabDrug

    375mg/m2 IV weekly (Wednesday) x 4 weeks (weeks 2-5)

Study groups in NCT00436904
Study groupRoleWhat they receive
Alemtuzumab + RituximabExperimentalAlemtuzumab 30mg Monday, Wednesday, and Friday x 5 weeks, Rituximab 375/mg/m2 IV weekly (Wednesday) x 4 weeks (weeks 2-5)
Receives: Drug: Alemtuzumab; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Confirmed Response, Defined as Objective Complete Remission or Partial Remission for a Duration of at Least 2 Months

    Confirmed response is defined as a > 50% decrease in clinical symptoms from baseline and recovery from blood counts.

    Measured: Up to 6 months

  2. Number of Participants With Treatment Related Adverse Events

    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

    Measured: Weekly for first 6 weeks, then monthly for 6 months, then at 9 and 12 months post registration

Secondary outcomes (4)

  1. Time to Response

    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.

    Measured: Registration to first response (up to 5 years)

  2. Duration of Response

    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.

    Measured: Up to 5 years

  3. Survival

    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.

    Measured: Death or last follow-up (up to 5 years)

  4. Time to Disease Progression

    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.

    Measured: Time from registration to progression (up to 5 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2007 (estimated)
  2. Study startDec 2004
  3. Primary completionJul 2008
  4. Study completionNov 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00436904
Sponsor's protocol ID
CDR0000529809
Other IDs
P30CA015083, MC038G, 801-04, 106.G0309, U3023s
Status last verified
Nov 2011
First submitted
15 Feb 2007
Last updated
1 Dec 2011
Data monitoring committee
Yes

Publications

  • Zent CS, Call TG, Shanafelt TD, Tschumper RC, Jelinek DF, Bowen DA, Secreto CR, Laplant BR, Kabat BF, Kay NE. Early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab. Cancer. 2008 Oct 15;113(8):2110-8. doi: 10.1002/cncr.23824.

    PubMed 18759253

  • Zent CS, Secreto CR, LaPlant BR, Bone ND, Call TG, Shanafelt TD, Jelinek DF, Tschumper RC, Kay NE. 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. 2008 Dec;32(12):1849-56. doi: 10.1016/j.leukres.2008.05.014. Epub 2008 Jun 27.

    PubMed 18584865

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alemtuzumab and Rituximab in people with Leukemia, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed Response, Defined as Objective Complete Remission or Partial Remission for a Duration of at Least 2 Months (time frame: Up to 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00436904, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2011.

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