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

NCT01203930 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 101-08
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 6

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.

Conditions

Chronic Lymphocytic Leukemia (CLL); Small Lymphocytic Lymphoma (SLL)

Keywords

CLL; SLL; GS-1101; CAL-101; Phosphatidylinositol 3-kinase (PI3K); Rituximab; Rituxan

Outcome Measures

Primary Outcomes (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.

  Up to 28 Months

Secondary Outcomes (9)

• Overall Safety of Idelalisib

  Up to 28 Months

• Lymphadenopathy Response Rate

  Baseline and up to 28 Months

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

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

• Duration of Response

  Up to 28 Months

• Progression-Free Survival

  Up to 28 Months

Study Arms (1)

Idelalisib

EXPERIMENTAL

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; Drug: Rituximab

Interventions

Idelalisib DRUG

Idelalisib 150 mg tablets administered orally twice daily

Also known as: Zydelig®, GS-1101, CAL-101

Idelalisib

Rituximab DRUG

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

Also known as: Rituxan

Idelalisib

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (6)

University of California, San Diego, Moores Cancer Center

La Jolla, California, 92093-0820, United States

Location

Stanford University School of Medicine

Stanford, California, 94304, United States

Location

Columbia University - Herbert Irving Pavilion

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The Universtity of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 26472751 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

idelalisib; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2010
• First Posted: September 17, 2010
• Study Start: October 1, 2010
• Primary Completion: August 1, 2015
• Study Completion: June 1, 2016
• Last Updated: November 16, 2018
• Results First Posted: May 22, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (6)