Difference between revisions of "Idelalisib (Zydelig)"
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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)]]== | ||
+ | |||
+ | ==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] | ||
+ | |||
+ | ==Idelalisib & Rituximab== | ||
+ | |||
+ | ===Regimen, Furman et al. 2014=== | ||
+ | <span | ||
+ | style="background:#00CD00; | ||
+ | padding:3px 6px 3px 6px; | ||
+ | border-color:black; | ||
+ | border-width:2px; | ||
+ | border-style:solid;">Phase III</span> | ||
+ | |||
+ | *[[Idelalisib (CAL-101)]] 150 mg PO BID | ||
+ | *[[Rituximab (Rituxan)]] 375 mg/m2 IV once on first dose, then 500 mg/m2 IV once on subsequent doses | ||
+ | |||
+ | '''Rituximab is given every two weeks x 5 doses then every three weeks x 3 doses for 8 doses, total.''' | ||
+ | |||
+ | '''Idelalisib continues until progression, and can be increased to 300 mg PO BID at that point.''' | ||
+ | |||
+ | ===References=== | ||
+ | # 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] | ||
+ | |||
+ | ==[[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== |
Revision as of 04:19, 28 January 2014
In clinical trials.
General information
Class/mechanism: Isoform-selective PI3K (phosphatidylinositol 3-kinase) inhibitor. CAL-101 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.[1][2][3]
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.
Diseases for which it is used
Chronic lymphocytic leukemia (CLL) and Small lymphocytic lymphoma (SLL)
Idelalisib (CAL-101)
Regimen, Gopal et al. 2014 (DELTA)
Phase II
- 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] link to original article contains verified protocol PubMed
Idelalisib & Rituximab
Regimen, Furman et al. 2014
Phase III
- Idelalisib (CAL-101) 150 mg PO BID
- Rituximab (Rituxan) 375 mg/m2 IV once on first dose, then 500 mg/m2 IV once on subsequent doses
Rituximab is given every two weeks x 5 doses then every three weeks x 3 doses for 8 doses, total.
Idelalisib continues until progression, and can be increased to 300 mg PO BID at that point.
References
- 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] link to original article contains verified protocol PubMed
Follicular lymphoma
Idelalisib (CAL-101)
Regimen, Gopal et al. 2014 (DELTA)
Phase II
- 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] link to original article contains verified protocol PubMed
Marginal zone lymphoma
Idelalisib (CAL-101)
Regimen, Gopal et al. 2014 (DELTA)
Phase II
- 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] link to original article contains verified protocol PubMed
Waldenström macroglobulinemia
Idelalisib (CAL-101)
Regimen, Gopal et al. 2014 (DELTA)
Phase II
- 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] link to original article contains verified protocol PubMed
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
No information available.
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
- ↑ 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