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Old 03-03-2007, 02:36 AM
gdpawel gdpawel is offline
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Default Clinical Trial of the DiSC Assay

Prospective, randomized trial of the DiSC Assay (chemosensitivity testing) in chronic lymphocytic leukemia (CLL) on response rate and survival.

The first prospective, randomized trial of the DiSC Assay (cell-death endpoint) is currently taking place in the United Kingdom (UK). It is part of a large trial in which 750 newly-diagnosed patients are being enrolled. The first goal of the study is simply a very traditional three-arm trial to compare three different forms of empiric chemotherapy in newly-diagnosed CLL. Patients are randomized to treatment with chlorambucil (Untreated Arm I), Fludarabine (Untreated Arm II), or Fludarabine + Cyclophosphamide (Untreated Arm III). Most CLL patients ultimately relapse (or have primary refractory disease) following first line therapy. Relapsing/refractory patients are then re-randomized to receive either DiSC Assay-directed chemotherapy (Refractory/Relapsed Arm I) or "standard," empiric therapy (Refractory/Relapsed Arm II).

Study details are described on the following web site and are excerpted below:

[url]http://www.clinicaltrials.gov/ct/sho...004218?order=1

Official Title: Phase III Randomized Study of Chlorambucil Alone Versus Fludarabine With or Without Cyclophosphamide in Patients With Newly Diagnosed Chronic Lymphocytic Leukemia

Study chair/Principal investigator

Daniel Catovsky, MD, Study Chair, Royal Marsden NHS Trust

Sponsored by

Leukemia Research Fund
Medical Research Council

Further Study Details:

OBJECTIVES:

Compare the survival rate of patients with newly diagnosed chronic lymphocytic leukemia treated with chlorambucil alone vs fludarabine with or without cyclophosphamide.

Compare the response rate and duration of remission in patients treated with these regimens.

Compare the toxic effects of these regimens in these patients.

Compare the quality of life of patients treated with these regimens.

Determine the impact of the drug response information provided by the DiSC assay on response rate and survival in relapsed or nonresponding patients.

Assess the prognostic value of five genetic markers: trisomy 12 and deletions at 11q23, 13q14, p53, and 6q21 in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients enter one of three treatment arms in the first randomization.Depending on response, some patients may also participate in a second randomization to one of two treatment arms.

Untreated Arm I: Patients receive oral chlorambucil daily for 7 days. Treatment repeats every 4 weeks until maximum response or up to 1 year.

Untreated Arm II: Patients receive fludarabine IV or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses.

Untreated Arm III: Patients receive cyclophosphamide IV and fludarabine IV for 3 days or orally daily for 5 days. Treatment repeats every 4 weeks for 3-8 courses. Patients who relapse after being in remission for at least 1 year may repeat the initial therapy or may participate in a second randomization. Patients who experience progressive disease or relapse within 1 year after treatment proceed to a second randomization.

Relapsed/Refractory Arm I: Treatment is guided by the results of the DiSC assay. Treatment may be one of the first-line treatments with fludarabine or standard CHOP chemotherapy repeated every 4 weeks (cyclophosphamide IV, doxorubicin IV, vincristine IV, and oral prednisolone on days 1-5) or any other therapy guided by the results of the DiSC assay.

Relapsed/Refractory Arm II: Treatment is physician's choice, which may include any of the options in arm I. Quality of life is assessed prior to initial therapy; at 3, 6, and 12 months; and then annually thereafter.

Patients are followed annually for survival.

PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study within 6-7 years.

Last edited by gdpawel : 07-08-2012 at 12:57 AM. Reason: correct url address
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Old 12-17-2012, 12:10 PM
gdpawel gdpawel is offline
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Default Chlorambucil Effective for CLL in Elderly

Will Boggs, M.D.

Chlorambucil is safe and effective for chronic lymphocytic leukemia (CLL) in older patients, according to data from sequential Cancer and Leukemia Group B (CALGB) studies.

Limited enrollment of older patients in pivotal trials of chemoimmunotherapy for CLL leaves open the question of what the best treatment is for these patients. Standard therapy for younger patients includes fludarabine and rituximab or fludarabine, cyclophosphamide, and rituximab, but two studies have suggested that chlorambucil plus rituximab is safe and effective in older CLL patients.

Dr. John C. Byrd from Ohio State University in Columbus and colleagues used data from four CALGB studies to examine the effects of chlorambucil, fludarabine, fludarabine plus rituximab, fludarabine with alemtuzumab consolidation, and fludarabine/rituximab with alemtuzumab consolidation on outcomes in patients aged 70 years and older.

In multivariable models, the estimated risk of progression did not differ significantly between chlorambucil and fludarabine for older patients. This was in contrast to the 40% decrease in the risk of progression when younger patients were treated with fludarabine.

Adding rituximab to fludarabine cut the risk of progression by 44% relative to fludarabine alone, and this effect was consistent across age groups. Adding alemtuzumab, however, did not improve progression-free survival over similar regimens without alemtuzumab, the researchers reported online December 10th in the Journal of Clinical Oncology.

Overall survival for patients 70 and older did not vary significantly across the treatment regimens.

The risk of death among older patients was estimated to be 45% higher with fludarabine than with chlorambucil, but this difference fell short of statistical significance.

As with progression-free survival, overall survival improved with the addition of rituximab to fludarabine, regardless of age, and there was little overall survival benefit with the addition of alemtuzumab consolidation.

"Chlorambucil is a reasonable chemotherapeutic backbone on which to design new combination regimens in this age group," the researchers conclude. "With recent data regarding the combination of chlorambucil and rituximab in older patients, this combination is certainly a standard therapeutic option for older patients and may be an ideal platform on which to add new targeted agents to improve efficacy."

Dr. Barbara F. Eichhorst from Uniklinik Koln, Koln, Germany was lead author of the report of the German CLL5 study but was not involved in this new analysis. She told Reuters Health in an email, "Chlorambucil is better than fludarabine in elderly patients. Fludarabine plus rituximab was better in comparison to fludarabine alone in both age groups. Because chemoimmunotherapies might be too toxic in elderly patients with comorbidity burden, results from studies for patients with higher comorbidity will show if less toxic chemoimmunotherapies are the new standard in this patients group as well."

"In Germany," she continued, "we favor (chlorambucil monotherapy) for patients with a high comorbidity burden, defined as a cumulative illness rating scale score >6. But based on the data of two phase II studies chlorambucil plus rituximab would be another option. We expect as new standard therapy in 2013 chlorambucil plus anti-CD20 antibody."

Chlorambucil Effective for Chronic Lymphocytic Leukemia in Elderly. Medscape. Dec 13, 2012.

J Clin Oncol 2012.

[url]http://jco.ascopubs.org/content/early/2012/12/04/JCO.2011.41.5646.abstract
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