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B-cell Chronic Lymphocytic LeukemiaPhase 2NCT00098670

Fludarabine, Rituximab, and Alemtuzumab in Treating Patients With Chronic Lymphocytic Leukemia

A Phase 2 study testing alemtuzumab, rituximab and fludarabine phosphate in people with B-cell Chronic Lymphocytic Leukemia and Stage I Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 2 sites 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

This phase II trial is studying how well giving fludarabine together with rituximab followed by alemtuzumab works in treating patients with chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
alemtuzumab, rituximab and fludarabine phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
2 sitesUnited States
Study dates
Oct 2004to Feb 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

Who may be able to join

  • Specific Diagnosis of B-Cell CLL
  • An absolute lymphocytosis of > 5,000/μL
  • Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes
  • Bone marrow examination must include at least a unilateral aspirate and biopsy; the aspirate smear must show > 30% of all nucleated cells to be lymphoid or the bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL; the overall cellularity must be normocellular or hypercellular
  • Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers; additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density; patients with bright surface immunoglobulin levels must have CD23 co-expression
  • Patients must be in the intermediate- or high-risk categories of the modified three-stage Rai staging system (i.e., stages I, II, III, or IV)
Show all 19Show fewer
  • Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least one of the following criteria:
  • Massive or progressive splenomegaly, hepatomegaly and/or lymphadenopathy;
  • Presence of weight loss > 10% over the preceding 6 month period;
  • Grade 2 or 3 fatigue;
  • Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of infection;
  • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months
  • No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
  • No medical condition requiring chronic use of oral corticosteroids
  • Performance Status 0 - 2
  • Due to alterations in host immunity, patients with HIV may not be enrolled
  • Due to the unknown teratogenic potential of alemtuzumab, pregnant or nursing women may not be enrolled; women and men of reproductive potential should agree to use an effective means of birth control
  • Creatinine =< 1.5 x upper limit of institutional normal value
  • Coomb's Testing NEGATIVE

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Cancer and Leukemia Group B

    Chicago, Illinois, 60606

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: A Phase II Study of Fludarabine + Rituximab Induction Followed by Alemtuzumab (Campath-1H, NSC #715969, IND #10864) Administered Subcutaneously as Consolidation in Untreated Patients With B-Cell Chronic Lymphocytic Leukemia

This phase II trial is studying how well giving fludarabine together with rituximab followed by alemtuzumab works in treating patients with chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others can find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fludarabine together with rituximab followed by alemtuzumab may kill more cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the rate of complete response and toxicity of concurrent treatment with fludarabine and rituximab followed by consolidative alemtuzumab in patients with previously untreated, but symptomatic, CLL.

II. To determine if alemtuzumab improves the CR rate with acceptable toxicity when administered as consolidation therapy following induction therapy with fludarabine and rituximab.

III. To estimate the progression-free and overall survival of high risk (VH gene unmutated and those with p53 dysfunction) and low-risk (others) patients following therapy with fludarabine and rituximab induction and consolidative alemtuzumab.

IV. To determine the frequency of molecular (PCR) remission following fludarabine and rituximab induction therapy and alemtuzumab consolidation therapy and if this serves as a surrogate marker for prolonged progression-free and overall survival.

SECONDARY OBJECTIVES:

  1. To determine the effect of concurrent treatment with fludarabine and rituximab followed by consolidative alemtuzumab on recovery of T-cells, NK cells, and serum immunoglobulin levels.

II. To determine clinical and molecular features that predict for poor response to fludarabine and rituximab induction and subsequent alemtuzumab consolidation therapy.

III. To assess preliminarily the molecular features of CLL at relapse in patients responding to chemoimmunotherapy for CLL.

IV. To determine the frequency of patients who remain at high risk for progression of CLL despite this therapy and who are thus eligible for nonmyeloablative stem cell transplantation studies such as CALGB 109901.

  1. To perform limited rituximab pharmacokinetics to determine the ideal schedule of administration for a subsequent rituximab maintenance treatment approach following induction therapy with fludarabine and rituximab.

OUTLINE:

Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.

Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.

Patients are followed at 2 months, every 3 months for 1 year, and then every 6 months for 7 years from study entry.

Being tested
alemtuzumab, rituximab, fludarabine phosphate
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

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

  • alemtuzumabBiological

    Also called anti-CD52 monoclonal antibody, Campath-1H, MoAb CD52, Monoclonal Antibody Campath-1H

    Given SC

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • fludarabine phosphateDrug

    Also called 2-F-ara-AMP, Beneflur, Fludara

    Given IV

Study groups in NCT00098670
Study groupRoleWhat they receive
Treatment (alemtuzumab, rituximab, fludarabine phosphate)ExperimentalPatients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression. Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.
Receives: Biological: alemtuzumab; Biological: rituximab; Drug: fludarabine phosphate

What is being measured

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

  1. Number of Participants With a Complete Response After Treatment With Fludarabine & Rituximab Followed by Alemtuzumab

    A complete response, as defined by the National Cancer Institute Working Group (NCIWG):

    • CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy

    Measured: Duration of treatment (up to 13.5 months)

Secondary outcomes (4)

  1. Number of Participants With a Complete or Partial Response After Induction Therapy With Fludarabine & Rituximab

    Response, as defined by the National Cancer Institute Working Group (NCIWG):

    CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy

    PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, >100,000/μL platelets, >11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions

    Measured: Up to 9 months

  2. 2 Year Progression Free Survival

    Percentage of patients who were alive and progression free at 2 years. The 2-year progression free survival was estimated using the Kaplan Meier method.

    Measured: 2 years from registration

  3. 2 Year Survival

    Percentage of participants who were alive at 2 years. The 2 year survival was estimated using the Kaplan Meier method.

    Measured: 2 years from registration

  4. Number of Participants With Severe Non-Hematologic Adverse Events During Treatment With Alemtuzumab

    The National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 2.0 was used to evaluate toxicity. Severe Adverse events are defined as grade 3, 4 or 5, at least possibly related to treatment.

    Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death.

    Measured: 6 weeks beginning at study week 36

Timeline

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

  1. First posted8 Dec 2004 (estimated)
  2. Study startOct 2004
  3. Primary completionFeb 2011
  4. Study completionFeb 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00098670
Sponsor's protocol ID
NCI-2012-02812
Other IDs
NCI-2012-02812, CDR0000398139, CALGB-10101, CALGB-10101, P30CA014236, U10CA031946
Status last verified
Dec 2012
First submitted
7 Dec 2004
Last updated
21 May 2014

Publications

  • Jones JA, Ruppert AS, Zhao W, Lin TS, Rai K, Peterson B, Larson RA, Marcucci G, Heerema NA, Byrd JC. Patients with chronic lymphocytic leukemia with high-risk genomic features have inferior outcome on successive Cancer and Leukemia Group B trials with alemtuzumab consolidation: subgroup analysis from CALGB 19901 and CALGB 10101. Leuk Lymphoma. 2013 Dec;54(12):2654-9. doi: 10.3109/10428194.2013.788179. Epub 2013 May 9.

    PubMed 23547837

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing alemtuzumab, rituximab and fludarabine phosphate in people with B-cell Chronic Lymphocytic Leukemia and Stage I Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 2 sites 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?

The sponsor lists 19 inclusion and 0 exclusion criteria. 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 21 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 3 Dec 2012). 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?

Number of Participants With a Complete Response After Treatment With Fludarabine & Rituximab Followed by Alemtuzumab (time frame: Duration of treatment (up to 13.5 months)). 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 NCT00098670, which also lists 1 linked publication.

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 21 May 2014.

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