Difference between revisions of "Idelalisib (Zydelig)"

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(FDA approval)
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==General information==
 
==General information==
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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.  Disruption of the various pathways regulated by PI3K is hypothesized to have therapeutic applications by affecting cellular metabolism, growth, oncogenesis, and survival.<ref name=insert>[http://www.gilead.com/~/media/Files/pdfs/medicines/oncology/zydelig/zydelig_pi.pdf Idelalisib (Zydelig) package insert]</ref><ref><ref>[[Media:Idelalisib.pdf | Idelalisib (Zydelig) package insert (locally hosted backup)]]</ref><ref>[http://zydelig.com/ Zydelig manufacturer's website]</ref><ref>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. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=83782 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.</ref><ref>I. W. Flinn, J. C. Byrd, R. R. Furman, J. R. Brown, T. S. Lin, C. Bello, N. A. Giese, A. S. Yu. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=34213 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.</ref><ref>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. [http://bloodjournal.hematologylibrary.org/content/117/2/591.full 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. [http://www.ncbi.nlm.nih.gov/pubmed/20959606 PubMed]</ref>
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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.<ref name=insert>[http://www.gilead.com/~/media/Files/pdfs/medicines/oncology/zydelig/zydelig_pi.pdf Idelalisib (Zydelig) package insert]</ref><ref>[[Media:Idelalisib.pdf | Idelalisib (Zydelig) package insert (locally hosted backup)]]</ref><ref>[http://zydelig.com/ Zydelig manufacturer's website]</ref><ref>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. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=83782 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.</ref><ref>I. W. Flinn, J. C. Byrd, R. R. Furman, J. R. Brown, T. S. Lin, C. Bello, N. A. Giese, A. S. Yu. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=65&abstractID=34213 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.</ref><ref>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. [http://bloodjournal.hematologylibrary.org/content/117/2/591.full 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. [http://www.ncbi.nlm.nih.gov/pubmed/20959606 PubMed]</ref>
 
<br>Route: PO
 
<br>Route: PO
 
<br>Extravasation: n/a
 
<br>Extravasation: n/a
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==Diseases for which it is used==
 
==Diseases for which it is used==
 
*[[Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL)]]
 
*[[Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL)]]
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==Idelalisib (CAL-101)==
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*[[Follicular lymphoma]]
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*[[Marginal zone lymphoma]]
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===Regimen, Gopal et al. 2014 (DELTA)===
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*[[Waldenström macroglobulinemia]]
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<span
 
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style="background:#EEEE00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase II</span>
 
−
 
 
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*[[Idelalisib (CAL-101)]] 150 mg PO BID
 
−
 
 
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'''Continued until progression, death, or unacceptable toxicity'''
 
−
 
 
−
===References===
 
−
# Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma. N Engl J Med. 2014 Jan 22. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1314583 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24450858 PubMed]
 
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# Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, Wagner-Johnston ND,Spurgeon SE, Kahl BS, Bello C, Webb HK, Johnson DM, Peterman S, Li D, Jahn TM, Lannutti BJ, Ulrich RG, Yu AS, Miller LL, Furman RR. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014 May 29;123(22):3390-7. Epub 2014 Mar 10. [http://bloodjournal.hematologylibrary.org/content/123/22/3390 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24615777 PubMed]
 
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==Idelalisib & Rituximab==
 
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===Regimen, Furman et al. 2014===
 
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<span
 
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style="background:#00CD00;
 
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padding:3px 6px 3px 6px;
 
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border-color:black;
 
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border-width:2px;
 
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border-style:solid;">Phase III</span>
 
−
 
 
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*[[Idelalisib (CAL-101)]] 150 mg PO BID
 
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*[[Rituximab (Rituxan)]] 375 mg/m2 IV once on first dose, then 500 mg/m2 IV once on subsequent doses
 
−
 
 
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'''Rituximab is given every two weeks x 5 doses then every three weeks x 3 doses for 8 doses, total.'''
 
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'''Idelalisib continues until progression, and can be increased to 300 mg PO BID at that point.'''
 
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===References===
 
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# Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, O'Brien SM. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2014 Jan 22. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1315226 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24450857 PubMed]
 
−
 
 
−
==[[Follicular lymphoma]]==
 
−
 
 
−
==Idelalisib (CAL-101)==
 
−
 
 
−
===Regimen, Gopal et al. 2014 (DELTA)===
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Idelalisib (CAL-101)]] 150 mg PO BID
 
−
 
 
−
'''Continued until progression, death, or unacceptable toxicity'''
 
−
 
 
−
===References===
 
−
# Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma. N Engl J Med. 2014 Jan 22. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1314583 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24450858 PubMed]
 
−
 
 
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==[[Mantle cell lymphoma]]==
 
−
 
 
−
==[[Marginal zone lymphoma]]==
 
−
 
 
−
==Idelalisib (CAL-101)==
 
−
 
 
−
===Regimen, Gopal et al. 2014 (DELTA)===
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Idelalisib (CAL-101)]] 150 mg PO BID
 
−
 
 
−
'''Continued until progression, death, or unacceptable toxicity'''
 
−
 
 
−
===References===
 
−
# Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma. N Engl J Med. 2014 Jan 22. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1314583 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24450858 PubMed]
 
−
 
 
−
==[[Waldenström macroglobulinemia]]==
 
−
 
 
−
==Idelalisib (CAL-101)==
 
−
 
 
−
===Regimen, Gopal et al. 2014 (DELTA)===
 
−
<span
 
−
style="background:#EEEE00;
 
−
padding:3px 6px 3px 6px;
 
−
border-color:black;
 
−
border-width:2px;
 
−
border-style:solid;">Phase II</span>
 
−
 
 
−
*[[Idelalisib (CAL-101)]] 150 mg PO BID
 
−
 
 
−
'''Continued until progression, death, or unacceptable toxicity'''
 
−
 
 
−
===References===
 
−
# Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma. N Engl J Med. 2014 Jan 22. [Epub ahead of print] [http://www.nejm.org/doi/full/10.1056/NEJMoa1314583 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24450858 PubMed]  
 
  
 
==Clinical trials==
 
==Clinical trials==
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==Patient drug information==
 
==Patient drug information==
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No information available.
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*Patient counseling information may be found in the [http://www.gilead.com/~/media/Files/pdfs/medicines/oncology/zydelig/zydelig_pi.pdf Idelalisib (Zydelig) package insert]<ref name="insert"></ref>
  
 
==History of changes in FDA indication==
 
==History of changes in FDA indication==
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<references/>
 
<references/>
  
 +
[[Category:Drug index]]
 +
[[Category:Chemotherapy]]
 
[[Category:Kinase inhibitors]]
 
[[Category:Kinase inhibitors]]
 
[[Category:PIK3CA inhibitors]]
 
[[Category:PIK3CA inhibitors]]
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[[Category:Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL) medications]]
 +
[[Category:Follicular lymphoma medications]]
 +
[[Category:Marginal zone lymphoma medications]]
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[[Category:Waldenström macroglobulinemia medications]]
 
[[Category:Drugs FDA approved in 2014]]
 
[[Category:Drugs FDA approved in 2014]]

Revision as of 04:21, 25 July 2014

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

Clinical trials

Patient drug information

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. ↑ 1.0 1.1 1.2 Idelalisib (Zydelig) package insert
  2. ↑ Idelalisib (Zydelig) package insert (locally hosted backup)
  3. ↑ Zydelig manufacturer's website
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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
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