Idelalisib (Zydelig)
General information
Class/mechanism: Isoform-selective PI3K (phosphatidylinositol 3-kinase) inhibitor. Idelalisib inhibits class I isoform p110 delta (p110δ), which is one of the mediators of activation of the PI3K pathway and is expressed at high levels by hematopoietic cells, particularly leukocytes. Inhibition of the PI3Kδ kinase pathway affects B-cell receptor (BCR), CXCR4, and CXCR5 signaling, disrupting trafficking and homing of B-cells to the lymph nodes and bone marrow. Lymphoma cells treated with idelalisib have been observed to have impaired chemotaxis, adhesion properties, and cell viability.[1][2][3][4][5][6]
Route: PO
Extravasation: n/a
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.[1]
Diseases for which it is used
- Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL)
- Follicular lymphoma
- Marginal zone lymphoma
- Waldenström macroglobulinemia
Clinical trials
- Efficacy and Safety Study of CAL-101 in Patients With Indolent B-Cell Non-Hodgkin Lymphoma (DELTA) (101-09)
- A Study of CAL-101 and Rituximab in Elderly Patients With Untreated CLL or SLL (101-08)
- Study to Investigate CAL-101 in Combination With Chemotherapeutic Agents and CD20 mAb in Patients With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
- An Extension Study for Patients Who Are Deriving Benefit With CAL-101 to Continue on Treatment at the End of the Current Study (101-99)
- Safety and Efficacy Study of CAL-101 in Patients With Previously Treated Low-grade Lymphoma
Patient drug information
- Patient counseling information may be found in the Idelalisib (Zydelig) package insert[1]
History of changes in FDA indication
- 7/23/2014: FDA approved "for the treatment of patients with:
- Relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.
- Relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies.
- Relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies."
Also known as
CAL-101, 5-fluoro-3-phenyl-2-[(S)-1-(9H-purin-6-ylamino)-propyl]-3H-quinazolin-4-one, GS 1101, GS-1101.
References
- ↑ 1.0 1.1 1.2 Idelalisib (Zydelig) package insert
- ↑ Idelalisib (Zydelig) package insert (locally hosted backup)
- ↑ Zydelig manufacturer's website
- ↑ S. E. Coutre, J. C. Byrd, R. R. Furman, J. R. Brown, D. M. Benson, N. D. Wagner-Johnston, I. W. Flinn, B. S. Kahl, S. E. F. Spurgeon, B. J. Lannutti, H. K. W. Hsu, R. Ulrich, S. Peterman, L. Holes, L. L. Miller, A. S. Yu. Phase I study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously treated chronic lymphocytic leukemia. 2011 ASCO Annual Meeting abstract 6631.
- ↑ I. W. Flinn, J. C. Byrd, R. R. Furman, J. R. Brown, T. S. Lin, C. Bello, N. A. Giese, A. S. Yu. Preliminary evidence of clinical activity in a phase I study of CAL-101, a selective inhibitor of the p1108 isoform of phosphatidylinositol 3-kinase (P13K), in patients with select hematologic malignancies. 2009 ASCO Annual Meeting abstract 3543.
- ↑ Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, Druker BJ, Puri KD, Ulrich RG, Giese NA. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011 Jan 13;117(2):591-4. Epub 2010 Oct 19. PubMed