Working… Menu

A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01203930
Recruitment Status : Terminated
First Posted : September 17, 2010
Results First Posted : May 22, 2017
Last Update Posted : November 16, 2018
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

This study is to evaluate the safety and clinical activity of idelalisib alone and in combination with rituximab in patients with CLL or SLL.

This Phase 2 study will be the first time that idelalisib is administered to previously untreated patients with hematologic malignancies. Idelalisib has demonstrated clinical activity as a single agent in relapsed or refractory CLL and SLL with acceptable toxicity, which supports its evaluation in previously untreated patients. The study population is limited to patients over 65 years of age because younger patients are generally appropriate for standard immunochemotherapy regimens that are highly active. Since the mechanism of action of idelalisib is distinct from rituximab, it is hypothesized that the combination will be more active than either agent alone. This study will establish initial safety and clinical activity of idelalisib in combination with rituximab in patients with CLL or SLL. Cohort 2 of this study will establish safety and clinical activity of idelalisib alone in subjects with untreated CLL or SLL.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL) Drug: Idelalisib Drug: Rituximab Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 105 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Single Arm Study to Investigate the Safety and Clinical Activity of Idelalisib Alone and in Combination With Rituximab in Elderly Subjects With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Actual Study Start Date : October 2010
Actual Primary Completion Date : August 2015
Actual Study Completion Date : June 2016

Arm Intervention/treatment
Experimental: Idelalisib
This arm consists of 2 cohorts. Participants in Cohort 1 will receive idelalisib for up to twelve 28-day cycles (or development of unacceptable toxicity) plus rituximab (8 doses through the end of Cycle 2). Upon completion of twelve 28-cycles, participants are eligible to remain on idelalisib in a continuation protocol. Participants in Cohort 2 will receive idelalisib until disease progression or development of unacceptable toxicity.
Drug: Idelalisib
Idelalisib 150 mg tablets administered orally twice daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101

Drug: Rituximab
Rituximab 375 mg/m^2 administered intravenously once weekly x 8 weeks
Other Name: Rituxan

Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 28 Months ]

    ORR was assessed based on standardized International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria as specifically modified for this study to reflect current recommendations which consider the mechanism of action of idelalisib and similar drugs, and was defined as the proportion of participants achieving a complete response (CR) or partial response (PR) as assessed by the investigator. Based on the CLL response definition in the protocol (modified Hallek 2008), the parameters of lymphadenopathy, liver and/or spleen size, constitutional symptoms, polymorphonuclear leukocytes, circulating clonal B-lymphocytes, platelet count, hemoglobin, and marrow were assessed.

    • CR: meeting all defined criteria
    • PR: meeting at least 2 of the criteria of circulating lymphocytes, lymphadenopathy, liver, spleen, or bone marrow (or only lymphadenopathy if liver and spleen normal at baseline) and at least 1 of the criteria for polymorphonuclear leukocytes, platelet count, or hemoglobin.

Secondary Outcome Measures :
  1. Overall Safety of Idelalisib [ Time Frame: Up to 28 Months ]
    The overall safety of idelalisib was assessed as the percentage of participants experiencing treatment-emergent adverse events (AEs; Serious AEs, Grade ≥ 3 AEs, AEs related to idelalisib, and AEs leading to discontinuation of idelalisib).

  2. Lymphadenopathy Response Rate [ Time Frame: Baseline and up to 28 Months ]
    Lymphadenopathy response rate was defined as the percentage of participants with a ≥ 50% reduction from baseline in the sum of the perpendicular diameters of all measurable lesions while receiving study therapy.

  3. Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of All Measurable Lesions [ Time Frame: Baseline; Weeks 8, 16, 24, 36, 48, 60, 72, 84, 96, 108, and 120 ]
  4. Duration of Response [ Time Frame: Up to 28 Months ]
    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.

  5. Progression-Free Survival [ Time Frame: Up to 28 Months ]

    Progression-free survival (PFS) was defined as the interval from the first dose date of drug to the earlier of the first documentation of definitive disease progression or death from any cause.

    Progression was defined using the Standardized IWCLL criteria as specifically modified for this study to consider the mechanism of action of idelalisib and similar drugs. The occurrence of any of the following events indicated progression:

    1. Evidence of any new disease
    2. Evidence of worsening of index lesions, spleen or liver, or non-index disease
    3. Decrease in platelet count or hemoglobin that is attributable to CLL and is confirmed by bone marrow biopsy

  6. Idelalisib Plasma Concentrations (Cohort 1) [ Time Frame: Predose and 1.5 hours postdose at Weeks 0, 4, and 24 ]
  7. Idelalisib Plasma Concentrations (Cohort 2) [ Time Frame: Predose and 1.5 hours postdose at Weeks 0 and 4 and predose at Weeks 8 and 20 ]
  8. Changes in Potential Pharmacodynamic Markers of Drug Activity in Plasma and Whole Blood [ Time Frame: Up to 169 days ]

    Changes in potential pharmacodynamic markers of drug activity will include assessments of chemokine and cytokine concentrations, effects on the activity of PI3K and related pathways, and effect on cell migration and other functional outcomes. This endpoint will be assessed at the following time points:

    • Idelalisib+Rituximab (Cohort 1): Predose and 1.5 hour postdose on Day 1 and predose on Days 15, 29, 57, 113, and 169
    • Idelalisib (Cohort 2): Predose on Days 1, 29, 57, 141

  9. Overall Survival [ Time Frame: Up to 28 Months ]
    Overall survival (OS) is defined as the interval from the start of study treatment to death from any cause.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Key Inclusion Criteria:

  • Histologically or cytologically confirmed CLL or SLL.
  • Age ≥ 65
  • Presence of measurable lymphadenopathy (defined as the presence of ≥1 nodal lesion that measures ≥ 1.5 cm in the longest diameter (LD) and ≥ 1.0 cm in the longest perpendicular diameter (LPD) as assessed by physical exam, computed tomography (CT) or magnetic resonance imaging (MRI)).
  • CLL - Binet Stage C or Rai Stage III or IV or has active disease defined by meeting at least one of the following criteria:

    • Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia
    • Massive (ie, > 6 cm below the left costal margin) or progressive or symptomatic splenomegaly
    • Massive nodes (ie, > 10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
    • Progressive lymphocytosis with an increase of more than 50% over a 2-month period or lymphocyte doubling time of less than 6 months
    • Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
    • At least one of the following disease-related symptoms:

      • Unintentional weight loss ≥ 10% within the previous 6 months
      • Significant fatigue
      • Fevers > 100.4 F for ≥ 2 weeks without other evidence of infection
      • Night sweats for ≥ 1 month without evidence of infection
  • SLL - has active disease as defined above for CLL, except the lymphocytosis criterion does not apply
  • World Health Organization (WHO) Performance Status of ≤ 2
  • For men of child-bearing potential, willing to use adequate methods of contraception for the entire duration of the study
  • Able to provide written informed consent

Key Exclusion Criteria:

  • Prior therapy for CLL or SLL, except corticosteroids for symptom relief
  • Treatment with a short course of corticosteroids for symptom relief within 1-week prior to Visit 1
  • Known active central nervous system involvement of the malignancy
  • Ongoing active, serious infection requiring systemic therapy. Patients may be receiving prophylactic antibiotics and antiviral therapy at the discretion of the treating physician.
  • Serum creatinine ≥ 2.0 mg/dL
  • Serum bilirubin ≥ 2 mg/dL (unless due to Gilbert's syndrome) or serum transaminases (ie, aspartate aminotransferase (AST), alanine aminotransferase (ALT)) ≥ 2 x upper limit of normal
  • Positive test for human immunodeficiency virus (HIV) antibodies
  • Active hepatitis B or C (confirmed by ribonucleic acid (RNA) test). Patients with serologic evidence of prior exposure are eligible.
  • History of a non-CLL malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to study entry, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01203930

Layout table for location information
United States, California
University of California, San Diego, Moores Cancer Center
La Jolla, California, United States, 92093-0820
Stanford University School of Medicine
Stanford, California, United States, 94304
United States, New York
Columbia University - Herbert Irving Pavilion
New York, New York, United States, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
The Universtity of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Gilead Sciences
Layout table for investigator information
Study Director: Gilead Study Director Gilead Sciences

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Gilead Sciences Identifier: NCT01203930     History of Changes
Other Study ID Numbers: 101-08
First Posted: September 17, 2010    Key Record Dates
Results First Posted: May 22, 2017
Last Update Posted: November 16, 2018
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gilead Sciences:
Phosphatidylinositol 3-kinase (PI3K)
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action