An Extension Study for Subjects Who Are Deriving Benefit With Idelalisib (GS-1101; CAL-101) Following Completion of a Prior Idelalisib Study

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

An Extension Study to Investigate the Safety and Durability of Clinical Activity of Idelalisib in Subjects With Hematologic Malignancies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01090414
• Other study ID #: 101-99
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 22, 2010
• Est. completion date: June 18, 2018

Study information

• Verified date: August 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a long-term safety extension study of idelalisib (GS-1101; CAL-101) in patients with hematologic malignancies who complete other idelalisib studies. It provides the opportunity for patients to continue treatment as long as the patient is deriving clinical benefit. Patients will be followed according to the standard of care as appropriate for their type of cancer. The dose of idelalisib will generally be the same as the dose that was administered at the end of the prior study, but may be titrated up to improve clinical response or down for toxicity. Patients will be withdrawn from the study if they develop progressive disease, unacceptable toxicity related to idelalisib, or if they no longer derive clinical benefit in the opinion of the investigator.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 202
• Est. completion date: June 18, 2018
• Est. primary completion date: June 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Patients with hematologic malignancies completing a prior idelalisib study with a clinical benefit are eligible

• Women of childbearing potential must have a negative pregnancy test to be eligible

• Male patients, and female patients of childbearing potential, must agree to use method(s) of contraception specified in the protocol

Key Exclusion Criteria:

• Patients who are unwilling or unable to comply with the protocol are not eligible

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Idelalisib
Idelalisib tablets or capsules administered orally

Locations

Country	Name	City	State
United States	Center for Cancer & Blood Disorders, PC	Bethesda	Maryland
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The Ohio State University Medical Center	Columbus	Ohio
United States	MD Anderson Cancer and Research Center	Houston	Texas
United States	MD Anderson Cancer Center	Houston	Texas
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	UCLA	Los Angeles	California
United States	University of Wisconsin	Madison	Wisconsin
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Long Island Jewish medical Center	New Hyde Park	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Weill Medical College of Cornell	New York	New York
United States	Stanford Cancer Center	Palo Alto	California
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon
United States	Yakima Regional Cancer Care	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (28)

Barrientos J, Coutre SE, et al. (2014). Long-Term Follow-Up of a Phase 1 Trial of Idelalisib (ZYDELIG®) in Combination with Bendamustine, Bendamustine/Rituximab, Fludarabine, Chlorambucil, or Chlorambucil/Rituximab in Patients with Relapsed or Refractory

Barrientos JC, Leonard JP, et al. (2013). Update on a Phase 1 Study of the Selective PI3Kd Inhibitor, Idelalisib (GS-1101) in Combination with Rituximab and/or Bendamustine in Patients with Relapsed or Refractory CLL [Presentation]. American Society for C

Barrientos JC, Sharman J, et al. (2012). GS-1101 (CAL-101), A Selective Phosphatidylinositol 3-Kinase-Delta Inhibitor, in Combination With Ofatumumab for the Treatment of Relapsed/ Refractory CLL [Abstract 1062]. Haematologica: the Hematology Journal 17th

Barrientos JC, Wagner-Johnston ND, et al. (2013). Chemo-Immunotherapy Combination of Idelalisib with Bendamustine/Rituximab or Chlorambucil/Rituximab in Patients with Relapsed/ Refractory CLL Demonstrates Efficacy and Tolerability [Poster 4176]. 55th ASH

Benson D, Kahl BS, et al. (2013). Final Results of a Phase 1 Study of Idelalisib, a Selective Inhibitor of PI3Kd, in Patients with Relapsed or Refractory Indolent non-Hodgkin Lymphoma [Presentation]. ASCO Annual Meeting, Chicago, Illinois.

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-k — View Citation

Brown JR, Cheson BD, et al. (2015). Patterns of Lymphocytosis in Patients with CLL or Small Lymphocytic Lymphoma (SLL) Treated with Idelalisib. 57th ASH Annual Meeting and Exposition, Orlando, Florida.

Brown JR, Furman RR, et al. (2013). Final Results of a Phase 1 Study of Idelalisib (GS-1101) a Selective Inhibitor of Phosphatidylinositol 3-Kinase p110 Delta (PI3Kd) in Patients with Relapsed or Refractory CLL [Presentation]. ASCO Annual Meeting, Chicago

Coutre S, Barrientos C, et al. (2015). Safety of Idelalisib in B-cell Malignancies: Integrated Analysis of Eight Clinical Trials. ASCO Annual Meeting, Chicago, Illinois.

Coutre S, Flinn I, et al. (2018). Idelalisib in Combination with Rituximab or Bendamustine or Both in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia. HemaSphere, 2:3.

Coutre S, Leonard J, et al. (2015). Idelalisib Monotherapy Results in Durable Responses in Patients with Relapsed or Refractory Waldenstrom's Macroglobulinemia. ASCO Annual Meeting, Chicago, Illinois.

DeVos S, Furman RR, et al. (2013). Idelalisib, a Selective Inhibitor of PI3Kd, in Combination with Bendamustine, Fludarabine, or Chlorambucil in Patients with Relapsed or Refractory (R/R) CLL [Poster 2878]. 55th ASH Annual Meeting and Exposition, New Orle

DeVos S, Wagner-Johnston ND, et al. (2014). Durable Responses Following Treatment with the PI3K-Delta Inhibitor Idelalisib in Combination with Rituximab, Bendamustine, or Both, in Recurrent Indolent non-Hodgkin Lymphoma: Phase I/II Results [Abstract 3063]

Flinn IW, Kahl BS, Leonard JP, Furman RR, Brown JR, Byrd JC, Wagner-Johnston ND, Coutre SE, Benson DM, Peterman S, Cho Y, Webb HK, Johnson DM, Yu AS, Ulrich RG, Godfrey WR, Miller LL, Spurgeon SE. Idelalisib, a selective inhibitor of phosphatidylinositol — View Citation

Furman R, DeVos S, et al. (2014). Long-Term Follow-Up of a Phase 1 Study of Idelalisib (ZYDELIG®) in Combination with Anti-CD20 Antibodies (Rituximab or Ofatumumab) in Patients with Relapsed or Refractory CLL. 56th ASH Annual Meeting and Exposition, San F

Furman R, Sharman J, et al. (2013). A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib and Rituximab for Previously Treated Patients with CLL [Abstract LBA-6]. 55th ASH Annual Meeting and Exposit

Ghia P, Cheson BD, et al. (2016). Patterns of Idelalisib Treatment-Emergent Lymphocytosis in Patients with CLL or SLL [poster]. EHA 21st Congress, Copenhagen, Denmark.

Ghia P, Coutre S, et al. (2016). Management of Transaminase Elevations Associated with Idelalisib [poster]. European Hematology Association (EHA) 21st Congress, Copenhagen, Denmark.

Gopal AK, Davies AJ, et al. (2015). Idelalisib Monotherapy and Durable Responses in Patients with Relapsed or Refractory SLL. 57th ASH Annual Meeting and Exposition, Orlando, Florida.

Kahl BS, Spurgeon SE, Furman RR, Flinn IW, Coutre SE, Brown JR, Benson DM, Byrd JC, Peterman S, Cho Y, Yu A, Godfrey WR, Wagner-Johnston ND. A phase 1 study of the PI3Kd inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL). — View Citation

Leonard JP, Wagner-Johnston ND, et al. (2013). Combinations of the PI3Kd Inhibitor Idelalisib (GS-1101) with Rituximab and/or Bendamustine are Tolerable and Highly Active in Patients with Previously Treated, Indolent non-Hodgkin Lymphoma: Updated Results

Martin P, Armas A, et al. (2015). Idelalisib Monotherapy and Durable Responses in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL). 57th ASH Annual Meeting and Exposition, Orlando, Florida.

O'Brien SM, Lamanna N, et al. (2013). A Phase 2 Study of the Selective Phosphatidylinositol 3-Kinase Delta (PI3Kd) Inhibitor Idelalisib (GS-1101) in Combination with Rituximab in Treatment-Naive Patients = 65 Years with CLL or SLL [Presentation]. ASCO Ann

O'Brien SM, Lamanna N, et al. (2014). Update on a Phase 2 Study of Idelalisib in Combination with Rituximab in Treatment-Naive Patients = 65 Years with CLL or SLL [Poster 1994]. 56th ASH Annual Meeting and Exposition, San Francisco, California.

O'Brien SM, Lamanna N, Kipps TJ, Flinn I, Zelenetz AD, Burger JA, Keating M, Mitra S, Holes L, Yu AS, Johnson DM, Miller LL, Kim Y, Dansey RD, Dubowy RL, Coutre SE. A phase 2 study of idelalisib plus rituximab in treatment-naïve older patients with chroni — View Citation

Spurgeon SE, Wagner-Johnston ND, et al. (2013). Final Results of a Phase 1 Study of Idelalisib, a Selective Inhibitor of Phosphatidylinositol 3-Kinase P110d (PI3Kd) in Patients with Relapsed or Refractory Mantle Cell Lymphoma [Presentation]. ASCO Annual M

Wagner-Johnston ND, DeVos S, et al. (2013). Preliminary Results of PI3Kd Inhibitor Idelalisib (GS-1101) Treatment in Combination with Everolimus, Bortezomib, or Bendamustine/Rituximab in Patients with Previously Treated Mantle Cell Lymphoma [Presentation]

Wierda W, Coutre S, et al. (2016). Management of Transaminase Elevations in Patients Receiving Idelalisib. ASCO Annual Meeting, Chicago, Illinois.

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Overall response rate (ORR) was defined as the percentage of participants who achieve complete response (CR), partial response (PR), or minor response (MR; for lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia (LPL/WM) only).	Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Primary	Percentage of Participants Who Experienced Any Treatment-Emergent Adverse Events		Parent study baseline to end of study 101-99 (maximum: up to 91.2 months) plus 30 days
Secondary	Duration of Response	Duration of response (DOR) was defined as the interval from the first documentation of CR, PR, or MR (for LPL/WM) to the earlier of the first documentation of disease progression or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.	Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Secondary	Progression-Free Survival	Progression-free survival (PFS) was defined as the interval from start of idelalisib treatment in the parent study to the earlier of the first documentation of disease progression or death from any cause. PFS was analyzed using KM estimates.	Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Secondary	Overall Survival	Overall survival (OS) was defined as the interval from the start of study treatment in the parent study to death from any cause. OS was analyzed using KM estimates.	Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)
Secondary	Time to Response	Time to response (TTR) was defined as the interval from start of study treatment to the first documentation of CR, PR, or MR (for LPL/WM). Analysis only includes participants who achieved complete or partial response (or minor response for LPL/WM participants). No participants in the 101-02 (AML and MM) groups achieved a complete or partial response.	Parent study baseline to end of study 101-99 (maximum: up to 91.2 months)