| City: |
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La Crosse |
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State:
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WI |
| Zip Code: |
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54601 |
| Conditions: |
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Leukemia |
| Purpose: |
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RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in
different ways to stop the growth of cancer cells, either by killing the cells or by
stopping them from dividing. Monoclonal antibodies, such as 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.
Lenalidomide may stimulate the immune system in different ways and stop cancer cells from
growing. Giving fludarabine and rituximab together with lenalidomide or cyclophosphamide may
kill more cancer cells.
PURPOSE: This randomized phase II trial is studying fludarabine and rituximab to compare how
well they work with or without lenalidomide or cyclophosphamide in treating patients with
symptomatic chronic lymphocytic leukemia.
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| Study summary: |
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OBJECTIVES:
Primary
- To determine the two-year progression-free survival (PFS) after remission induction
(RI) with four different chemo-immunotherapy combinations for patients with untreated,
symptomatic, lower-risk and high-risk chronic lymphocytic leukemia (CLL) to decide
which of the four arms, if any, to take forward into a randomized phase III trial.
Secondary
- To determine the induction response to fludarabine phosphate and rituximab (FR) and
fludarabine phosphate, cyclophosphamide, and rituximab (FCR) in each of these arms,
along with the consolidation response to lenalidomide in patients with CLL.
- To determine the toxicity from these four chemoimmunotherapy combinations and that of
consolidation therapy with lenalidomide.
- To determine the induction response and toxicity of FCR in patients with del(11q22.3)
along with consolidation response, 2-year PFS and toxicity of lenalidomide in this
specific genetic group.
- To determine the effect of pretreatment biologic characteristics on clinical outcomes,
such as attaining a complete response to induction therapy and progression-free
survival.
- To collect relapse samples to determine the frequency of clonal evolution among
patients with IgVH mutated and unmutated disease and to study mechanisms of resistance
to chemoimmunotherapy.
- To determine if flow cytometry-negative status immediately post-therapy and at 24
months after study entry is an effective surrogate marker for prolonged
progression-free survival and overall survival.
OUTLINE: This is a multicenter study. Patients are stratified according to risk group
(intermediate vs high). Patients are randomized to 1 of 3 treatment arms or assigned to arm
IV if found to be del(11q22.3) positive.
- Arm I (remission-induction [RI] therapy with fludarabine and rituximab): Patients
receive rituximab IV on days 1, 3, and 5 of course 1 and on day 1 of all subsequent
courses. Patients also receive fludarabine phosphate IV over 30 minutes or orally on
days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease
progression.
- Arm II (RI therapy with fludarabine and rituximab followed by remission-consolidation
[RC] therapy with lenalidomide): Patients undergo RI therapy as in arm I. Patients with
a complete or partial response or stable disease proceed to RC therapy beginning
approximately 4 months after completion of RI, comprising oral lenalidomide once daily
on days 1-21. Treatment repeats every 28 days for 3-6 courses in the absence of disease
progression.
- Arm III (RI therapy with fludarabine phosphate, rituximab, and cyclophosphamide):
Patients receive rituximab IV on days 1 and 3 of course 1 and on day 1 of all
subsequent courses. Patients also receive fludarabine phosphate IV over 30 minutes or
orally followed by cyclophosphamide IV over 30 minutes on days 1-3. Treatment repeats
every 28 days for up to 6 courses in the absence of disease progression.
- Arm IV [del(11q22.3)-positive] (RI therapy with fludarabine, rituximab, and
cyclophosphamide followed by RC therapy with lenalidomide): Patients undergo the first
course of RI therapy as in arm I or II, followed by rituximab IV on day 1 of all
subsequent courses, and fludarabine IV over 30 minutes and cyclophosphamide IV over 30
minutes on days 1-3. Treatment repeats every 28 days for up to 6 courses in the absence
of disease progression. Beginning approximately 4 months after completion of RI
therapy, patients receive RC therapy comprising oral lenalidomide as in arm II.
Patients undergo bone marrow aspirate and blood sample collection at baseline; 3 months
after completion of RI therapy; 2 months after completion of lenalidomide consolidation
therapy (arm II and IV only); 2 years after study enrollment; and then at the time of
relapse. Samples are assessed for interphase cytogenetic abnormalities; clonal evolution;
IgV_H gene mutational status; CD38, CD49d, and ZAP-70 expression; p53 dysfunction, gene
expression profile, and epigenetic changes in methylation. Samples are also assessed for
flow cytometry negativity status. Studies include fluorescence in situ hybridization,
chromosomal translocation, flow cytometry, and cytogenetics.
After completion of study therapy, patients are followed every 3 months for 1 year and then
every 6 months for up to 15 years. |
| Criteria: |
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DISEASE CHARACTERISTICS:
- Diagnosis of B-cell chronic lymphocytic leukemia (CLL) meeting the following
criteria:
- Absolute lymphocytosis > 5,000/μL
- Lymphocytes must appear mature with < 55% prolymphocytes
- Bone marrow aspirate smear must show > 30% of all nucleated cells as being
lymphoid OR bone marrow core biopsy must show lymphoid infiltrates compatible
with marrow involvement by CLL
- Overall cellularity must be normocellular or hypercellular
- Lymphocyte phenotype must reveal predominant B-cell monoclonal population
sharing a B-cell marker (i.e., CD19, CD20, or CD23) with the CD5 antigen, in the
absence of other pan-T-cell markers
- B-cells must be monoclonal with regard to expression of either kappa or
lambda light chains and have surface immunoglobulin expression of low
density
- Patients with bright surface immunoglobulin levels must have CD23
coexpression
- Must have symptomatic, active disease and meet 1 of the following risk criteria
according to the modified three-stage Rai staging system:
- Intermediate-risk disease (i.e., Rai stage I or II) with 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% within the past 6 months
- Grade 2 or 3 fatigue
- Fevers > 100.5° F or night sweats for > 2 weeks without evidence of
infection
- Progressive lymphocytosis with an increase of > 50% over a 2-month period
or an anticipated doubling time of < 6 months
- High-risk disease (i.e., Rai stage III or IV)
- Concurrent participation on CALGB-20702 (Leukemia Correlative Studies) required
PATIENT CHARACTERISTICS:
- Performance status 0-2
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use two effective methods of contraception for ≥ 4 weeks prior
to, during, and for ≥ 4 weeks after completion of lenalidomide therapy (for patients
randomized to arm II or IV)
- Creatinine ≤ 1.5 times upper limit of normal
- No medical condition requiring chronic use of oral corticosteroids
- Patients with HIV infection may be eligible provided they meet the following
criteria:
- CD4-positive cell count > 350/mm³
- HIV viral load < 10,000 copies HIV RNA/mL (if not on anti-HIV therapy) OR < 50
copies HIV RNA/mL (if on anti-HIV therapy)
- No evidence of hepatitis B or C infection
- No evidence of resistant strains of HIV
- No history of AIDS-defining condition
PRIOR CONCURRENT THERAPY:
- No prior therapy for CLL, including corticosteroids for autoimmune complications that
have developed since the initial diagnosis of CLL
- No concurrent zidovudine or stavudine
- No concurrent hormones or other chemotherapy, except steroids for hypersensitivity
reactions or new adrenal failure or hormones for non-disease-related conditions
(e.g., insulin for diabetes)
- No concurrent chronic oral steroids
- No concurrent palliative radiotherapy
- No concurrent epoetin alfa or darbepoetin alfa during remission consolidation therapy
(for patients randomized to arm II or IV)
- Concurrent participation on CALGB-9665 allowed |
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| Study is available at: |
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Gundersen Lutheran Center for Cancer and Blood
La Crosse, WI 54601
United States
Primary Contact:
Clinical Trials Office - Gundersen Lutheran Cancer Center
Email: cancerctr@gundluth.org
Phone: 608-775-2385 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 22, 2011 |
Modifications to
this listing: |
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above to view all information about this clinical trial. |
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