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A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

Publication ,  Journal Article
Willis, CR; Goodrich, A; Park, K; Waselenko, JK; Lucas, M; Reese, A; Diehl, LF; Grever, MR; Byrd, JC; Flinn, IW
Published in: Ann Hematol
May 2006

In an attempt to exploit bcl-2 overexpression and aberrant p53 function, two frequently encountered aberrations that predict marked treatment resistance and worse prognosis in patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), we combined theophylline, pentostatin, and chlorambucil at two dose levels (cohort I: 30 mg/m(2); cohort II: 20 mg/m(2)) on a 21-day cycle for up to six courses. We employed a phase I/II design to determine feasibility, define the maximum tolerated dose (MTD), and explore the impact of biologic modulation on response and time to progression (TTP) in 20 patients with relapsed or refractory CLL and NHL. Eight patients were enrolled in cohort I. They demonstrated a response rate (RR) of 28% and a 16.5-month TTP after receiving a median of two cycles. A 50% RR was observed in this cohort when patients with adverse histologies were excluded. Because of myelotoxicity, this dose level defined the MTD, and de-escalation occurred. All 12 patients in cohort II received 20 mg/m(2) chlorambucil. A 50% RR and an 18-month TTP were observed after a median of 5.5 cycles. An RR of 47% and a complete remission (CR) of 5% were observed for the entire group, although responses and TTP varied greatly by histology. Significant activity was observed in patients with B-cell CLL and follicular lymphoma (FL). RR and TTP for fludarabine-sensitive/naïve and fludarabine-refractory (FR) B-cell CLL patients were 66 vs 25% and 20 vs 8.5 months, respectively. Both FL patients responded (one with partial remission and one with CR), with a 22.5-monthly median TTP. For responding patients, median TTP and overall survival (OS) was 21 and 69 months, respectively, compared to a median TTP of 2 months and an OS of 13.5 months for nonresponders. The combination of pentostatin, chlorambucil, and theophylline is the active regimen in patients with FL and B-cell CLL.

Duke Scholars

Published In

Ann Hematol

DOI

ISSN

0939-5555

Publication Date

May 2006

Volume

85

Issue

5

Start / End Page

301 / 307

Location

Germany

Related Subject Headings

  • Theophylline
  • Survival Rate
  • Remission Induction
  • Recurrence
  • Pentostatin
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Lymphoma, Non-Hodgkin
  • Leukemia, Lymphocytic, Chronic, B-Cell
 

Citation

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MLA
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Willis, C. R., Goodrich, A., Park, K., Waselenko, J. K., Lucas, M., Reese, A., … Flinn, I. W. (2006). A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Ann Hematol, 85(5), 301–307. https://doi.org/10.1007/s00277-005-0025-9
Willis, Carl R., Amy Goodrich, Kathy Park, Jamie K. Waselenko, Margaret Lucas, Amy Reese, Louis F. Diehl, Michael R. Grever, John C. Byrd, and Ian W. Flinn. “A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma.Ann Hematol 85, no. 5 (May 2006): 301–7. https://doi.org/10.1007/s00277-005-0025-9.
Willis CR, Goodrich A, Park K, Waselenko JK, Lucas M, Reese A, et al. A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Ann Hematol. 2006 May;85(5):301–7.
Willis, Carl R., et al. “A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma.Ann Hematol, vol. 85, no. 5, May 2006, pp. 301–07. Pubmed, doi:10.1007/s00277-005-0025-9.
Willis CR, Goodrich A, Park K, Waselenko JK, Lucas M, Reese A, Diehl LF, Grever MR, Byrd JC, Flinn IW. A phase I/II study examining pentostatin, chlorambucil, and theophylline in patients with relapsed chronic lymphocytic leukemia and non-Hodgkin's lymphoma. Ann Hematol. 2006 May;85(5):301–307.
Journal cover image

Published In

Ann Hematol

DOI

ISSN

0939-5555

Publication Date

May 2006

Volume

85

Issue

5

Start / End Page

301 / 307

Location

Germany

Related Subject Headings

  • Theophylline
  • Survival Rate
  • Remission Induction
  • Recurrence
  • Pentostatin
  • Middle Aged
  • Maximum Tolerated Dose
  • Male
  • Lymphoma, Non-Hodgkin
  • Leukemia, Lymphocytic, Chronic, B-Cell