Study to Investigate Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 Monoclonal Antibody (mAb) in Participants With Relapsed or Refractory Indolent B-cell Non-Hodgkin's Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase I Study to Investigate the Safety and Clinical Activity of Idelalisib in Combination With Chemotherapeutic Agents, Immunomodulatory Agents and Anti-CD20 mAb in Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma, Mantle Cell Lymphoma or Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01088048
• Other study ID #: 101-07
• Status: Completed
• Phase: Phase 1
• Start date: March 25, 2010
• Est. completion date: April 28, 2015

Study information

• Verified date: February 2021
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to evaluate the safety of idelalisib in combination with an anti-CD20 monoclonal antibody (mAb), a chemotherapeutic agent, a mammalian target of rapamycin (mTOR) inhibitor, a protease inhibitor, an antiangiogenic agent, and/or an immunomodulatory agent in participants with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL), or chronic lymphocytic leukemia (CLL).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 241
• Est. completion date: April 28, 2015
• Est. primary completion date: April 28, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Age = 18

• Previously treated with relapsed or refractory disease (refractory defined as not responding to a standard regimen or progressing within 6 months of the last course of a standard regimen)

• Disease status requirement:

• For CLL patients, symptomatic disease that mandates treatment as defined by the International Workshop on Chronic Lymphocytic Lymphoma (IWCLL) 2008 criteria

• For indolent NHL and MCL patients, measurable disease by CT scan defined as at least 1 lesion that measures > 2 cm in a single dimension

• WHO performance status of = 2

• For men and women of child-bearing potential, willing to use adequate contraception (ie, latex condom, cervical cap, diaphragm, abstinence, etc.) for the entire duration of the study.

• For Cohort 7 only: Women of child bearing potential must have 2 negative pregnancy tests prior to starting lenalidomide.

• Able to provide written informed consent

Key Exclusion Criteria:

• Is not a good candidate to receive any of the drugs administered in the study for a given disease (idelalisib, bendamustine, rituximab, ofatumumab, fludarabine, everolimus, bortezomib, or chlorambucil), according to the clinical judgment of the investigator

• Patients with atypical immunophenotype with t(11:14) translocation or cyclin D1 over-expression (CLL patients only)

• Had radiotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product within 4-weeks prior to the baseline disease status tests

• Had treatment with a short course of corticosteroids for symptom relief within 1-week prior to the baseline disease status tests

• Has had an allogeneic hematopoietic stem cell transplant

• Has known active central nervous system involvement of the malignancy

• Is pregnant or nursing

• Has active, serious infection requiring systemic therapy. Patients may receive prophylactic antibiotics and antiviral therapy at the discretion of the investigator

• Has absolute neutrophil count (ANC) < 1000/µL, unless it is related to underlying CLL, MCL or indolent NHL, the latter documented by > 50% infiltration of bone marrow by tumor cells

• Has platelet count < 75000/µL, unless it is related to underlying CLL, MCL, or iNHL, the latter documented by > 50% infiltration of bone marrow by tumor cells

• Has serum creatinine = 2.0 mg/dL

• For Cohort 7 only: Has creatinine clearance < 60 mL/min

• Has serum bilirubin = 2 mg/dL (unless due to Gilbert's syndrome) for patients with iNHL or CLL; for patients with MCL, serum bilirubin = 1.5 x upper limit of normal

• Has serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) = 2 x upper limit of normal

• Has Child-Pugh Class B or C hepatic impairment

• Has a positive test for HIV antibodies

• Has active hepatitis B or C (confirmed by RNA test). Patients with serologic evidence of prior exposure are eligible.

• Prior treatment with idelalisib

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

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Indolent Non-Hodgkin's Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Mantle Cell Lymphoma

Intervention

Drug:
• Idelalisib
Idelalisib tablet administered orally
• Rituximab
Rituximab administered intravenously
• Bendamustine
Bendamustine administered intravenously
• Ofatumumab
Ofatumumab administered intravenously
• Fludarabine
Fludarabine administered orally
• Everolimus
Everolimus administered orally twice daily until disease progression
• Bortezomib
Bortezomib administered as a subcutaneous injection
• Chlorambucil
Chlorambucil administered on Days 1-7 every 28 days to allow appropriate therapy for participants with CLL and to coordinate into a cycle period equivalent to other study treatment regimens.
• Lenalidomide
Lenalidomide administered orally

Locations

Country	Name	City	State
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	MD Anderson Cancer	Houston	Texas
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	UCLA	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Weill Medical College of Cornell	New York	New York
United States	Stanford Cancer Center	Palo Alto	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon
United States	North Star Lodge Cancer Center	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (13)

Barrientos J, Coutre S, de Vos S, et al. Long-term follow-up of a Phase 1 study evaluating the selective PI3K-delta inhibitor idelalisib in combination with bendamustine (B), bendamustine/rituximab (BR), fludarabine (F), chlorambucil (Chl), Or chlorambuci

Barrientos J, Leonard J, Furman R, Flinn I, De Vos S, Coutre S, et al. Phase 1b study of idelalisib (GS-1101) plus chlorambucil ± rituximab in patients with relapsed and refractory chronic lymphocytic leukemia (CLL). European Hematology Association (EHA)

Barrientos J, Sharman J, De Vos S, et al. GS-1101 (CAL-101), selective phosphatidylinositol 3-Kinase inhibitor, in combination with ofatumumab for treatment of relapsed/refractory chronic lymphocytic leukemia. European Hematology Association (EHA) 2012 Co

Barrientos JC, Coutre SE, de Vos S, et al. Long-term follow-up of a Phase 1b trial of idelalisib in combination with chemoimmunotherapy in patients with relapsed/refractory chronic lymphocytic leukemia including patients with del17p/TP53 mutation. 51st An

Coutre S, Leonard J, Furman R, et al. Combinations of the selective phosphatidylinositol 3 Kinase-delta (PI3Kd) inhibitor GS-1101 (CAL-101) with rituximab and/or bendamustine are tolerable and highly active in patients with relapsed or refractory chronic

de Vos S, Schreeder M, Finn I, et al. A phase 1 study of the selective phosphatidylinositol 3 Kinase-delta (PI3Kd) inhibitor CAL-101 (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory indolent non-Hodgkin l

de Vos S, Wagner-Johnston N, Coutre S, et al. 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. Society of H

Flinn I, Schreeder M, Coutre S, et al. A phase 1 study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-Kinase P110d, in combination with anti-CD20 monoclonal antibody therapy and/or bendamustine in patients with previously treated B-c

Flinn I, Schreeder M, Wagner-Johnson N, et al. A phase 1 study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-Kinase P110d, in combination with rituximab and/or bendamustine in patients with relapsed or refractory B-cell malignancies

Fowler N, de Vos S, Schreeder M, et al. Combinations of the phosphatidylinositol 3 Kinase delta (PI3Kd) inhibitor idelalisib (GS-1101) with rituximab and/or bendamustine are tolerable and highly active in previously treated, indolent non-Hodgkin lymphoma:

Furman R, Barrientos J, Sharman J, et al. A phase 1/2 study of the selective phosphatidylinositol 3-Kinase-delta (PI3Kd) inhibitor CAL-101 (GS-1101) with ofatumumab in patients with previously treated chronic lymphocytic leukemia (CLL). [Poster 6518] 2012

Sharman J, de Vos S, Leonard J, et al. A phase 1 study of the selective phosphatidylinositol 3-Kinase-delta (PI3Kd) inhibitor CAL-101 (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory chronic lymphocytic l

Wagner-Johnston ND, De Vos S, Leonard J, Sharman JP, Schreeder MT, Boccia RV, et al. Preliminary results of PI3Kd inhibitor idelalisib (GS-1101) treatment in combination with everolimus, bortezomib, or bendamustine/rituximab in patients with previously tr

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of Exposure to IDELA	Duration of exposure to IDELA was summarized using descriptive statistics.	First dose date up to 12 months
Primary	Toxicity of Administration of IDELA	Percentage of participants experiencing toxicities of administration of IDELA were measured according to the Common Terminology Criteria for Adverse Events v4.02	First dose date up to 5 years
Secondary	Overall Response Rate	Overall Response Rate (ORR) was defined as the percentage of participants achieving a complete response (CR) or partial response (PR).; The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL),2008; iNHL & MCL: Cheson, 2007	Up to 5 years
Secondary	Duration of Response	Duration of response (DOR) was defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of disease progression or death from any cause.	Up to 5 years
Secondary	Time to Response	Time to response (TTR) was defined as the interval from the start of study drug to the first documentation of CR or PR.	Up to 5 years
Secondary	Progression-free Survival	Progression free survival (PFS) was defined as the interval from the start of study drug to the earlier of the first documentation of disease progression or death from any cause.; The response definitions were based on the following standard criteria established for each indication: CLL: International Workshop on chronic lymphocytic leukemia (IWCLL), 2008; iNHL & MCL: Cheson, 2007	Up to 5 years
Secondary	Overall Survival	Overall Survival (OS) was defined as the interval from the start of study drug to death from any cause.	Up to 5 years
Secondary	Plasma Concentration of IDELA (Cohort 1, Cohorts 2 and 3, Cohort 5)		Predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 0; predose, 1.5 hours postdose at Weeks 4, 12, and 24
Secondary	Plasma Concentration of IDELA (Cohort 4)		Predose at Week 0; predose, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 hours postdose at Week 4; predose, 1.5 hours postdose at Week 12; and predose, 1.5 hours postdose at Week 24
Secondary	Plasma Concentration of IDELA (Cohort 6)		Predose, 1.5 hours postdose at Weeks 0, 4, 12 and 24
Secondary	Plasma Concentration of IDELA (Cohort 7)		Predose, 1.5 hours postdose at Weeks 0, 5 and 13
Secondary	Sub-study: Plasma Concentration of IDELA (Cohorts 1-4)		pre dose and 0.5, 1, 1.5, 2.0, 3.0, 4.0, and 6.0 hours post dose
Secondary	Plasma Concentration of Bendamustine		Predose, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 hours postdose at Week 0
Secondary	Plasma Concentration of Everolimus		Predose, 1.5 hours postdose at Weeks 0 and 4
Secondary	Plasma Concentration of Lenalidomide		Predose, 1.5 hours postdose at Week 1 and predose at Week 5