AzTrials
AzTrials

Chronic Lymphocytic Leukemia (CLL)Phase 2NCT01203930

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

A Phase 2 study testing Idelalisib and Rituximab in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by Gilead Sciences at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 65 years and older
What is being tested?
Idelalisib and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
105 participants
Where
6 sitesUnited States
Study dates
Oct 2010to Jun 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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
Show all 18Show fewer
  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • The Universtity of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California, San Diego, Moores Cancer Center

    La Jolla, California, 92093-0820

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Columbia University - Herbert Irving Pavilion

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Stanford University School of Medicine

    Stanford, California, 94304

Other trials in United States

About this study

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

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.

Being tested
Idelalisib, Rituximab
Keywords
CLL, SLL, GS-1101, CAL-101, Phosphatidylinositol 3-kinase (PI3K), Rituximab, Rituxan
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IdelalisibDrug

    Also called Zydelig®, GS-1101, CAL-101

    Idelalisib 150 mg tablets administered orally twice daily

  • RituximabDrug

    Also called Rituxan

    Rituximab 375 mg/m^2 administered intravenously once weekly x 8 weeks

Study groups in NCT01203930
Study groupRoleWhat they receive
IdelalisibExperimentalThis 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.
Receives: Drug: Idelalisib; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    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.

    Measured: Up to 28 Months

Secondary outcomes (9)

  1. Overall Safety of Idelalisib

    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).

    Measured: Up to 28 Months

  2. Lymphadenopathy Response Rate

    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.

    Measured: Baseline and up to 28 Months

  3. Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of All Measurable Lesions

    Measured: Baseline; Weeks 8, 16, 24, 36, 48, 60, 72, 84, 96, 108, and 120

  4. 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.

    Measured: Up to 28 Months

  5. Progression-Free Survival

    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

    Measured: Up to 28 Months

  6. Idelalisib Plasma Concentrations (Cohort 1)

    Measured: Predose and 1.5 hours postdose at Weeks 0, 4, and 24

  7. Idelalisib Plasma Concentrations (Cohort 2)

    Measured: 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

    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

    Measured: Up to 169 days

  9. Overall Survival

    Overall survival (OS) is defined as the interval from the start of study treatment to death from any cause.

    Measured: Up to 28 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2010 (estimated)
  2. Study startOct 2010
  3. Primary completionAug 2015
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01203930
Sponsor's protocol ID
101-08
Status last verified
May 2017
First submitted
15 Sep 2010
Last updated
16 Nov 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.

Publications

  • 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-naive older patients with chronic lymphocytic leukemia. Blood. 2015 Dec 17;126(25):2686-94. doi: 10.1182/blood-2015-03-630947. Epub 2015 Oct 15.

    PubMed 26472751

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Idelalisib and Rituximab in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by Gilead Sciences at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to 28 Months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01203930, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Nov 2018.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in