A Randomized, Double-Blind, Placebo-Controlled Study of Idelalisib in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia (CLL)

• ClinicalTrials.gov Identifier: NCT01539512
• Recruitment Status: Completed
• First Posted: February 27, 2012
• Results First Posted: October 16, 2014
• Last Update Posted: May 14, 2019
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

This Phase 3, randomized, double-blind, placebo-controlled study is to evaluate the effect of idelalisib in combination with rituximab on the onset, magnitude, and duration of tumor control in participants previously treated for chronic lymphocytic leukemia (CLL). Eligible patients will be randomized with a 1:1 ratio into 1 of the 2 treatment arms to receive either idelalisib plus rituximab or placebo plus rituximab. Participants who are tolerating primary study therapy but experience definitive CLL progression are eligible to receive active idelalisib therapy in the extension study, GS-US-312-0117.

Condition or disease	Intervention/treatment	Phase
Chronic Lymphocytic Leukemia	Drug: Idelalisib; Drug: Rituximab; Drug: Placebo to match idelalisib	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib (GS-1101) in Combination With Rituximab for Previously Treated Chronic Lymphocytic Leukemia
• Study Start Date: April 2012
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Idelalisib + rituximab; Participants will receive idelalisib plus rituximab	Drug: Idelalisib; Idelalisib 150 mg tablet administered orally twice daily; Other Names: Zydelig®; GS-1101; CAL 101; Drug: Rituximab; Rituximab administered intravenously 8 times through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter; Other Name: Rituxan®
Placebo Comparator: Placebo + rituximab; Participants will receive placebo to match idelalisib plus rituximab	Drug: Rituximab; Rituximab administered intravenously 8 times through Week 20: Day 1: 375 mg/m^2, and 500 mg/m^2 thereafter; Other Name: Rituxan®; Drug: Placebo to match idelalisib; Placebo to match idelalisib administered orally twice daily

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival [ Time Frame: Up to 17 months ]
   Progression-free survival was defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause. Definitive disease progression was CLL progression based on standard criteria (other than lymphocytosis alone) as defined by the 2008 update of the International Workshop on CLL guidelines, ie, appearance of any new lesion; increase by ≥ 50% in the sum of the products of the perpendicular diameters of measured lymph nodes (SPD); new or ≥ 50% enlargement of liver or spleen; transformation to a more aggressive histology (eg, Richter's or prolymphocytic transformation); reduction in the number of blood cells (cytopenia) attributable to CLL.

Secondary Outcome Measures :

1. Overall Response Rate [ Time Frame: Up to 17 months ]

   Overall response rate was defined as the percentage of participants who achieved a best overall response of complete response or partial response.

   Complete response was defined as no lymphadenopathy, hepatomegaly, splenomegaly; normal complete blood count; confirmed by bone marrow aspirate & biopsy.

   Partial response was defined as >1 of the following criteria: a 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver size, spleen size; plus ≥ 1 of the following: ≥ 1500/μL absolute neutrophil count, > 100000/μL platelets, > 11.0 g/dL hemoglobin or 50% improvement for either of these parameters without transfusions or growth factors.

2. Lymph Node Response Rate [ Time Frame: Up to 17 months ]
   Lymph node response rate was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the SPD of index lymph nodes.
3. Overall Survival [ Time Frame: Up to 17 months ]
   Overall survival was defined as the interval from randomization to death from any cause.
4. Complete Response Rate [ Time Frame: Up to 17 months ]
   Complete response rate was defined as the percentage of participants who achieved a complete response.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion:

• Adult subjects with previously treated recurrent CLL who have measurable lymphadenopathy
• Require therapy for CLL
• Have experienced CLL progression < 24 months since the completion of the last prior therapy
• Currently not sufficiently fit to receive cytotoxic therapy because of chemotherapy-induced bone marrow damage or comorbidities.

Contacts and Locations

  Show 72 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Thomas Jahn, MD; Gilead Sciences

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, O'Brien SM. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014 Mar 13;370(11):997-1007. doi: 10.1056/NEJMoa1315226. Epub 2014 Jan 22.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01539512 History of Changes
• Other Study ID Numbers: GS-US-312-0116; 2011-005180-24 ( EudraCT Number )
• First Posted: February 27, 2012
• Results First Posted: October 16, 2014
• Last Update Posted: May 14, 2019
• Last Verified: April 2015

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 http://www.gilead.com/research/disclosure-and-transparency.
• 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.
• URL: http://www.gilead.com/research/disclosure-and-transparency

Keywords provided by Gilead Sciences:

CLL; CAL-101; GS 1101; PI3K; GS-US-312-0117; idelalisib

Additional relevant MeSH terms:

Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Rituximab; Idelalisib; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action