Study design in chronic lymphocytic leukemia

Recent enthusiasm for clinical trials in chronic lymphocytic leukemia (CLL) has resulted from both an increase in our understanding of the biology of CLL, and the availability of new and active cytotoxic drugs (e.g. 2'-deoxycoformycin [DCF]; fludarabine monophosphate [FAMP]) and the development of interesting biologic agents (e.g. IL-2). To best identify regimens worth pursuing in large scale clinical trials, uniform eligibility, response and toxicity criteria are essential. Standardization will facilitate comparison of results, ensure homogeneity of patient groups on clinical trials, and minimize the arbitrary nature of dose modifications. In 1987, an NCI-sponsored Working Group (NCI-WG) developed Guidelines for US clinical trials for CLL which included specific eligibility, response and toxicity criteria. These will be modified over time as more is learned about the disease. Trials are currently restricted to patients with active B-CLL. Although complete and partial response are carefully defined, alternative systems (e.g. stage shift for partial response) may be tested concurrently and definitions revised if warranted. Similarly, use of the modified Rai staging is encouraged, although other systems may also be studied and compared for clinical relevance. The U.S. Cooperative Oncology Groups and Cancer Centers are participating in a National CLL treatment program following the NCI-WG Guidelines. Phase I and II pilot trials of DCF and FAMP combined with each other or with conventional agents (e.g. FAMP + chlorambucil [CLB] + prednisone [P]; DCF + CLB + P; FAMP + P) are being conducted in previously treated patients. A collaborative phase III trial will compared the most promising regimens with "standard" chemotherapy in untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)