Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia.
BACKGROUND
The safety and efficacy of the interleukin-2 diphtheria toxin fusion protein (DAB(389)IL2; denileukin diftitox) directed against the IL-2 receptor (IL-2R) was tested in patients with recurrent or refractory chronic lymphocytic leukemia (CLL).


METHODS
Denileukin diftitox was administered as 60-minute intravenous infusions for 5 days every 21 days at a dose of 18 mug/kg per day for up to 8 cycles. In total, 28 patients were treated in 2 multiinstitutional studies with similar eligibility criteria and treatment protocols. Twenty-two patients receive > or = 2 cycles of denileukin diftitox and were evaluable for response.


RESULTS
Twelve of 22 patients achieved reductions of peripheral CLL cells, with 5 of 12 patients achieving >80% reductions. Six of 22 patients achieved reductions in the size of lymph node on examination and computed tomography scans, and all 6 of those patients met the criteria for a partial or complete response that lasted > or = 2 months. Bone marrow biopsies before and after treatment confirmed a complete remission that lasted for 1 year in 1 patient. Overall, denileukin diftitox produced complete remission in 1 of 22 patients (4%) and partial remission in 5 of 22 patients (23%) for a total remission rate of 27%. Progression-free intervals in the responders were 2 months in 2 patients and 4 months, 6 months, 7 months, and 12 months in 1 patient each. Toxicities were moderate. No infections associated with immunosuppression were seen. There was no significant correlation of response or toxicities with the numbers of denileukin diftitox cycles received or with CD25 levels.


CONCLUSIONS
Follow-up studies will be required to identify predictors of response that may improve the response rate to denileukin diftitox in patients with CLL.
Department of Medicine, Scott and White Hospital, Temple, Texas 76508, USA. afrankel@swmail.sw.org
Arthur E
AE
Frankel
Asha
A
Surendranathan
Jennifer H
JH
Black
Angela
A
White
Kristen
K
Ganjoo
Larry D
LD
Cripe
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001707:Biopsy, Needle; D001853:Bone Marrow / Q000473:pathology; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment; D016879:Salvage Therapy; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox