Exclusion from Acute Myeloid Leukemia (AML) Clinical Trials of Patients Unlikely To Respond.

Abstract

Introduction: Patients with newly diagnosed AML are increasingly being enrolled on industry-sponsored clinical trials. These trials routinely exclude patients with Zubrod performance status (PS) >2, bilirubin >1.9 mg/dL, or creatinine >1.9 mg/dL; such patients are well-known to be relatively unlikely to respond (UTR). Here we quantify the effect of this practice on inclusion of UTR patients in clinical trials. Patients and Methods: Overall, 2323 adults with newly-diagnosed AML (no acute promyelocytic leukemia) were registered on clinical trials (industry-sponsored and other) from 1991–2006. Considering patients as UTR if they fulfilled any of the criteria noted above, we examined rates of enrollment of UTR patients over time: Results: Thus, while more patients are being enrolled on clinical trials, fewer UTR patients are being enrolled particularly over the last 5 years (p = .04) with a concomitant decrease in the proportion of such patients enrolled (p<.0001 over the 16 years in question). Findings are qualitatively the same in older patients. Conclusion: Newer clinical trials may be less applicable to UTR patients than previous trials. There is a need for clinical trials specific to the UTR population, the group most in need of novel therapies. Rates of enrollement of unlikely to respond patients on clinical trials for newly diangosed AML Year No. of pts. treated on clinical trial (pts. age≥60 yrs) UTR pts. enrolled (pts. age≥60 yrs) % of UTR pts. enrolled (pts. age ≥60 yrs) 1991 101 (50) 17 (13) 17 (26) 1992 100 (48) 20 (14) 20 (29) 1993 96 (46) 18 (9) 19 (20) 1994 109 (41) 23 (13) 21 (32) 1995 102 (48) 20 (10) 20 (21) 1996 104 (63) 14 (10) 13 (16) 1997 145 (81) 30 (20) 21 (25) 1998 124 (63) 14 (8) 11 (13) 1999 164 (86) 26 (16) 16 (19) 2000 169 (96) 25 (19) 15 (20) 2001 187 (98) 30 (19) 16 (19) 2002 162 (91) 17 (11) 10 (12) 2003 195 (111) 4 (2) 2 (2) 2004 184 (109) 17 (11) 9 (10) 2005 185 (117) 15 (7) 8 (6) 2006 196 (109) 17 (12) 9 (11) Total 2323 (1257) 307 (194) 13 (15)