Efficacy and Safety of Idelalisib in Combination With Ofatumumab for Previously Treated Chronic Lymphocytic Leukemia

Phase 3

Terminated

• Conditions: Chronic Lymphocytic Leukemia
• Interventions: Drug: Idelalisib; Drug: Ofatumumab

• Registration Number: NCT01659021
• Lead Sponsor: Gilead Sciences

Brief Summary

The primary objective of this study is to evaluate the effect of the addition of idelalisib to ofatumumab on progression-free survival (PFS) in participants with previously treated chronic lymphocytic leukemia (CLL).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-08-03
• Study First Submitted QC: 2012-08-03
• Study First Posted: 2012-08-07
• Study Start: 2012-12-04
• Disposition First Submitted: 2015-11-05
• Disposition First Submitted QC: 2015-11-05
• Disposition First Posted: 2015-12-04
• Results First Submitted: 2017-02-14
• Results First Submitted QC: 2017-02-14
• Results First Posted: 2017-03-31
• Primary Completion: 2018-08-15
• Study Completion: 2018-08-15
• Status Verified: 2019-08
• Last Update Submitted: 2019-08-05
• Last Update Posted: 2019-08-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 261

Inclusion Criteria

• Adults 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
• Have disease that is not refractory to ofatumumab

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Idelalisib+ofatumumab	Idelalisib	Randomized Initial Therapy (24 weeks): Idelalisib + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation. Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.
Ofatumumab	Ofatumumab	Randomized Initial Therapy (24 weeks): Ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 2000 mg weekly for 7 weeks, and then 2000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Observation until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation. Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.
Idelalisib+ofatumumab	Ofatumumab	Randomized Initial Therapy (24 weeks): Idelalisib + ofatumumab for a total of 12 infusions (300 mg on Day 1, followed by 1000 mg weekly for 7 weeks, and then 1000 mg every 4 weeks for 4 doses) Continuing Therapy/Observation: Idelalisib 150 mg tablets twice daily until the earliest of participant withdrawal from study, definitive progression of CLL, intolerable idelalisib-related toxicity, pregnancy or initiation of breast feeding, substantial noncompliance with study procedures, or study discontinuation. Long-Term Follow-up: Participants were followed for up to 5 years. Information on medical status, anti-tumor treatments, secondary malignancies, and survival status were collected annually during a routine clinic visit or other contact, such as telephone.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival	Randomization to End of Study (up to 60 months)	Progression-free survival (PFS) 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. PFS was analyzed using Kaplan-Meier (KM) estimates.

Secondary Outcome Measures

Name	Time	Method
Complete Response Rate	Randomization to End of Study (up to 60 months)	Complete response rate was defined as the percentage of participants who achieve a complete response and maintain their response for at least 8 weeks (with a 1-week window).
Overall Response Rate	Randomization to End of Study (up to 60 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. Overall response rate was analyzed using KM estimates.
Overall Survival	Randomization to Last Long-Term Follow-Up Visit (up to maximum of 5 years)	Overall survival was defined as the interval from randomization to death from any cause. Overall survival was analyzed using KM estimates.
Progression-Free Survival in Subgroup of Participants With Chromosome 17p Deletion and/or TP53 Mutation	Randomization to End of Study (up to 60 months)	Progression-free survival in subgroup of participants with chromosome 17p deletion and/or TP53 mutation was analyzed using KM estimates.
Lymph Node Response Rate	Randomization to End of Study (up to 60 months)	Lymph node response rate was defined as the proportion of participants who achieved a ≥ 50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lymph nodes.

Trial Locations

Locations (78)

City of Hope; 🇺🇸 Duarte, California, United States

California Cancer Associates for Research and Excellence (CCARE); 🇺🇸 Fresno, California, United States

Kaiser Permanente; 🇺🇸 San Diego, California, United States

Coastal Integrative Cancer Care; 🇺🇸 San Luis Obispo, California, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Kaiser Permanente Vallejo Medical Center; 🇺🇸 Vallejo, California, United States

Kaiser Permanente of Colorado; 🇺🇸 Denver, Colorado, United States

Saint Mary's Regional Cancer Center; 🇺🇸 Grand Junction, Colorado, United States

Cancer Specialists of North Florida; 🇺🇸 Jacksonville, Florida, United States

Georgia Regents University; 🇺🇸 Augusta, Georgia, United States

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