Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
| Phase | Type | Status | Age | Sponsor | Protocol IDs |
|---|---|---|---|---|---|
| Phase III | Treatment | Completed | 18 and over | NCI | CLB-9011 CAN-NCIC-CL1, E-C9011, SWOG-9108, CALGB-9011, CL1 |
Objectives
I. Compare progression-free survival of previously untreated patients with intermediate- and high-risk (Rai Stages I-IV) B-cell chronic lymphocytic leukemia (CLL) randomly assigned to treatment with chlorambucil vs. fludarabine, with crossover for patients who fail initial therapy. II. Compare the quality of life (measured by the need for transfusion, incidence of infection, and performance status) of patients on these 2 regimens. III. Determine, by use of a crossover design, whether fludarabine and chlorambucil are cross-resistant. IV. Compare overall survival on these 2 regimens based on "intent to treat" for the crossover.
Entry Criteria
Disease Characteristics:
Previously untreated B-cell chronic lymphocytic leukemia (CLL)
defined by presence of all of the following criteria:
Lymphocytosis at least 5,000 for at least 4 weeks or
lymphocytosis greater than 100,000 at diagnosis
Morphologically mature-appearing lymphocytes
Normocellular or hypercellular bone marrow with more than 30%
of lymphoid nucleated cells
Blood lymphocyte immunophenotype mostly B-cell by appropriate
marker studies, e.g.:
sIg+, CD19+, CD20+, CD24+ with CD5+ OR
Kappa or lambda light chain and low cell surface density
expression of sIg
Intermediate- or high-risk disease (Rai Stages I-IV) required
Intermediate-risk disease must be active, evident by at least
one of the following criteria:
At least one of the following disease-related symptoms:
More than 10% weight loss during the preceding 6 months
Extreme fatigue
Temperature more than 100 F for more than 2 weeks with no
evidence of infection
Night sweats
Massive or progressive splenomegaly and/or lymphadenopathy
Progressive lymphocytosis with an increase of more than 50%
over preceding 2 months or an anticipated doubling time of
less than 12 months
No lymphoproliferative disorder other than B-cell CLL allowed
Negative direct Coombs' test required
No uncontrolled bacterial, viral, or fungal infections
No clinical autoimmune disease (e.g., AIHA, ITP)
SWOG patients must submit bone marrow aspirates and
peripheral blood for immunophenotyping and
molecular/cytogenetic studies
ECOG patients must be concurrently enrolled on protocol
EST-6491 for flow cytometric and bcl-2 expression studies
Prior/Concurrent Therapy:
No prior cytotoxic therapy Prior steroids for immune problems (e.g., AIHA, ITP) allowed No concurrent corticosteroids
Patient Characteristics:
Age:
At least 18
Performance status:
CALGB 0-2
Hematopoietic:
See Disease Characteristics
Hepatic:
Bilirubin no more than 2.0 mg/dl
SGOT/SGPT no more than 1.5 x normal
Renal:
Creatinine no more than 1.5 x normal
BUN no more than 1.5 x normal
Other:
No second malignancy within 5 years except:
Inactive nonmelanomatous skin cancer
In situ carcinoma of the cervix
No serious medical illness that would limit survival to
less than 2 years
No psychiatric conditions that would preclude informed
consent
No pregnant women
Effective contraception required of fertile women
Expected Enrollment
538 patients will be entered; as of June 3, 1994, accrual is expected to be complete in about 8 months.
Outline
Randomized study. Crossover design for Arms I and II only. Arm I: Single-Agent Chemotherapy. Fludarabine, FAMP, NSC-312887. Arm II: Single-Agent Chemotherapy. Chlorambucil, CLB, NSC-3088. Arm III (arm closed as of 4/28/94): 2-Drug Combination Chemotherapy. FAMP; CLB.Published Results
Solh M, Rai KR, Peterson BL, et al.: The impact of initial fludarabine therapy on transformation to Richter syndrome or prolymphocytic leukemia in patients with chronic lymphocytic leukemia: analysis of an intergroup trial (CALGB 9011). Leuk Lymphoma 54 (2): 252-4, 2013.[PUBMED Abstract]
Martell RE, Peterson BL, Cohen HJ, et al.: Analysis of age, estimated creatinine clearance and pretreatment hematologic parameters as predictors of fludarabine toxicity in patients treated for chronic lymphocytic leukemia: a CALGB (9011) coordinated intergroup study. Cancer Chemother Pharmacol 50 (1): 37-45, 2002.[PUBMED Abstract]
Morrison VA, Rai KR, Peterson BL, et al.: Therapy-related myeloid leukemias are observed in patients with chronic lymphocytic leukemia after treatment with fludarabine and chlorambucil: results of an intergroup study, cancer and leukemia group B 9011. J Clin Oncol 20 (18): 3878-84, 2002.[PUBMED Abstract]
Morrison VA, Rai KR, Peterson BL, et al.: Impact of therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup Study Cancer and Leukemia Group B 9011. J Clin Oncol 19 (16): 3611-21, 2001.[PUBMED Abstract]
Rai KR, Peterson BL, Appelbaum FR, et al.: Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med 343 (24): 1750-7, 2000.[PUBMED Abstract]
Morrison V, Rai K, Peterson B, et al.: Therapy-related myelodysplastic syndrome (T-MDS) or acute myeloid leukemia (T-AML) in patients with chronic lymphocytic leukemia (CLL) treated with chlorambucil (F+C): an Intergroup Study. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A29, 9a, 1999.
Morrison A, Rai R, Peterson B, et al.: Impact of therapy with chlorambucil, fludarabine or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: an Intergroup Study (CALGB 9011). [Abstract] Blood 92 (10 suppl 1): A-2020, 490a, 1998.
Rai KR, Peterson B, Elias L, et al.: A randomized comparison of fludarabine and chlorambucil for patients with previously untreated chronic lymphocytic leukemia: a CALGB, SWOG, CTG/NCI-C, and ECOG Intergroup study. [Abstract] Blood 88 (10 suppl 1): A-552, 141a, 1996.
Rai KR, Peterson B, Kolitz J, et al.: Fludarabine induces a high complete remission rate in previously untreated patients with active chronic lymphocytic leukemia (CLL): a randomized inter-group study. [Abstract] Blood 86 (10, Suppl 1): A-607, 2414, 1995.
Related PublicationsMorrison VA, Peterson BL, Rai KR, et al.: Alemtuzumab increases serious infections in patients with previously untreated chronic lymphocytic leukemia (CLL) receiving fludarabine-based therapy: a comparative analysis of 3 Cancer and Leukemia Group B studies (CALGB 9011, 9712, 19901). [Abstract] Blood 110 (11): A-756, 2007.
Byrd JC, Rai K, Peterson BL, et al.: Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011. Blood 105 (1): 49-53, 2005.[PUBMED Abstract]
Hsi ED, Kopecky KJ, Appelbaum FR, et al.: Prognostic significance of CD38 and CD20 expression as assessed by quantitative flow cytometry in chronic lymphocytic leukaemia. Br J Haematol 120 (6): 1017-25, 2003.[PUBMED Abstract]
Trial Lead Organizations
Cancer and Leukemia Group B
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| Kanti Rai, MD, Protocol chair | |
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NCIC-Clinical Trials Group
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| Lois Shepherd, MD, Protocol chair | |
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Southwest Oncology Group
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| Laurence Elias, MD, Protocol chair (Contact information may not be current) | |
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Eastern Cooperative Oncology Group
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| John Hines, MD, Protocol chair (Contact information may not be current) | |
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Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.
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