Idelalisib (Zydelig)

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.
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.

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

1. 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
2. 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. link to original article 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

1. 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

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

1. 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 (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

1. 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 (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

1. 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.