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:
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.