Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia

Arthur E. Frankel, Asha Surendranathan, Jennifer H. Black, Angela White, Kristen Ganjoo, Larry Cripe

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

BACKGROUND. The safety and efficacy of the interleukin-2 diphtheria toxin fusion protein (DAB339IL2; 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 μg/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 ≥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 >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.

Original languageEnglish
Pages (from-to)2158-2164
Number of pages7
JournalCancer
Volume106
Issue number10
DOIs
StatePublished - May 15 2006

Fingerprint

Diphtheria Toxin
B-Cell Chronic Lymphocytic Leukemia
Proteins
denileukin diftitox
Clinical Studies
Interleukin-2 Receptors
Clinical Protocols
Intravenous Infusions
Immunosuppression

Keywords

  • Chronic lymphocytic leukemia
  • Interleukin-2 receptor
  • Progression-free interval
  • Response evaluation
  • Toxin conjugates
  • Vascular leak syndrome

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia. / Frankel, Arthur E.; Surendranathan, Asha; Black, Jennifer H.; White, Angela; Ganjoo, Kristen; Cripe, Larry.

In: Cancer, Vol. 106, No. 10, 15.05.2006, p. 2158-2164.

Research output: Contribution to journalArticle

Frankel, Arthur E. ; Surendranathan, Asha ; Black, Jennifer H. ; White, Angela ; Ganjoo, Kristen ; Cripe, Larry. / Phase II clinical studies of denileukin diftitox diphtheria toxin fusion protein in patients with previously treated chronic lymphocytic leukemia. In: Cancer. 2006 ; Vol. 106, No. 10. pp. 2158-2164.
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AU - Ganjoo, Kristen

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N2 - BACKGROUND. The safety and efficacy of the interleukin-2 diphtheria toxin fusion protein (DAB339IL2; 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 μg/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 ≥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 >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.

AB - BACKGROUND. The safety and efficacy of the interleukin-2 diphtheria toxin fusion protein (DAB339IL2; 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 μg/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 ≥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 >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.

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KW - Interleukin-2 receptor

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KW - Response evaluation

KW - Toxin conjugates

KW - Vascular leak syndrome

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