Clinical trial NCT01203930: A Study of Idelalisib and Rituximab in Elderly Patients With Untreated CLL or SLL
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Keywords: CLL
SLL
GS-1101
CAL-101
Phosphatidylinositol 3-kinase (PI3K)
Rituximab
Rituxan
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2010-09-17
Enrollment: 105
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 28 Months
Secondary outcomes:
measure: Overall Safety of Idelalisib
timeFrame: Up to 28 Months
measure: Lymphadenopathy Response Rate
timeFrame: Baseline and up to 28 Months
measure: Percent Change From Baseline in the Sum of the Product of the Greatest Perpendicular Diameters (SPD) of All Measurable Lesions
timeFrame: Baseline; Weeks 8, 16, 24, 36, 48, 60, 72, 84, 96, 108, and 120
measure: Duration of Response
timeFrame: Up to 28 Months
measure: Progression-Free Survival
timeFrame: Up to 28 Months
measure: Idelalisib Plasma Concentrations (Cohort 1)
timeFrame: Predose and 1.5 hours postdose at Weeks 0, 4, and 24
measure: Idelalisib Plasma Concentrations (Cohort 2)
timeFrame: Predose and 1.5 hours postdose at Weeks 0 and 4 and predose at Weeks 8 and 20
measure: Changes in Potential Pharmacodynamic Markers of Drug Activity in Plasma and Whole Blood
timeFrame: Up to 169 days
measure: Overall Survival
timeFrame: Up to 28 Months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California, San Diego, Moores Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: New York
country: United States
facility: Columbia University - Herbert Irving Pavilion
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The Universtity of Texas MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.