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NCT01282424: DELTA

Efficacy and Safety Study of Idelalisib in Participants With Indolent B-Cell Non-Hodgkin Lymphomas

Completed Phase 2 Results posted Last updated 11 July 2019
What this trial tests

Phase 2 trial testing Idelalisib in Follicular Lymphoma in 125 participants. Completed in 16 May 2018.

Timeline
18 March 2011
Primary endpoint
2 May 2018
16 May 2018

Quick facts

Lead sponsorGilead Sciences
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment125
Start date18 March 2011
Primary completion2 May 2018
Estimated completion16 May 2018
Sites41 locations across France, Italy, United Kingdom, Germany, Poland, United States

Drugs / interventions tested

Conditions studied

Sponsor

Gilead Sciences — full company profile →

Who can join

18 and older, any sex, with Follicular Lymphoma or Small Lymphocytic Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate Primary · Start of Treatment to End of Treatment (up to 81 months)

Overall response rate (ORR) was assessed based on the International Working Group Revised Response Criteria for Malignant Lymphoma (Cheson, 2007), and was defined as the percentage of participants achieving a complete response (CR) or partial response (PR; or minor response \[MR\] for participants with WM) as assessed by the study independent review committee (IRC). CR was defined as the complete resolution of all disease-related radiological abnormalities and the disappearance of all signs and symptoms related to the disease. PR was defined as a ≥ 50% reduction in the sum of the products of

GroupValue95% CI
Idelalisib57.648.4 – 66.4
Duration of Response Secondary · Start of Treatment to End of Treatment (up to 81 months)

Duration of Response (DOR) was defined as the interval from the first documentation of CR or PR (or MR for participants with WM) to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. DOR was analyzed using Kaplan-Meier (KM) estimates.

GroupValue95% CI
Idelalisib12.56.2 – 28.6
Lymph Node Response Rate Secondary · Start of Treatment to End of Treatment (up to 81 months)

Lymph node response (LNR) was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline in the sum of the product of the perpendicular diameters (SPD) of measurable index lesions as assessed by the study IRC.

GroupValue95% CI
Idelalisib56.847.6 – 65.6
Time to Response Secondary · Start of Treatment to End of Treatment (up to 81 months)

Time to response (TTR) was defined as the interval from the start of idelalisib treatment to the first documentation of CR or PR (or MR for participants with WM) as assessed by the study IRC.

GroupValue95% CI
Idelalisib2.01.8 – 4.2
Progression-Free Survival Secondary · Start of Treatment to End of Treatment (up to 81 months)

Progression-free survival (PFS) was defined as the interval from the start of idelalisib treatment to the earlier of the first documentation of disease progression as assessed by the study IRC or death from any cause. PFS was analyzed using KM estimates.

GroupValue95% CI
Idelalisib11.18.3 – 14.0
Overall Survival Secondary · Start of Treatment to Last Long-Term Follow-Up Visit (up to maximum of 7 years)

Overall survival (OS) was defined as the time interval from the start of idelalisib treatment to death from any cause. OS was analyzed using KM estimates.

GroupValue95% CI
Idelalisib48.633.9 – 71.7
Change in Health-Related Quality of Life Using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) Secondary · Baseline to End of Treatment (up to 81 months)

Change in health-related quality of life events were reported by participants using the Functional Assessment of Cancer Therapy: Lymphoma Subscale (FACT-LymS) assessment tool. Results are presented as the mean (SD) best change from baseline. The best change from baseline was defined as the highest change score (improvement) after baseline. The FACT-LymS is on a scale from 0-60, with higher scores associated with a better quality of life. It incorporates values from 15 questions, each rated 0-4, related to study indications.

GroupValue95% CI
Idelalisib10.3± 17.08
Change in Karnofsky Performance Status Secondary · Baseline to End of Treatment (up to 81 months)

The change in Karnofsky performance status was reported as the best (highest change score) and worst (lowest change score) change from baseline using the Karnofsky performance criteria. The Karnofsky score classified participants according to their functional impairment. Scores are on a scale from 0-100, the lower the score, the worse the survival for most serious illnesses.

Best change
GroupValue95% CI
Idelalisib3.0± 8.71
Worst change
GroupValue95% CI
Idelalisib-10.7± 12.61
Safety and Tolerability of Idelalisib Assessed as the Number of Participants Experiencing Adverse Events (AEs) or Abnormalities in Vital Signs, Laboratory Tests, or Electrocardiograms Secondary · Start of Treatment to End of Treatment (up to 81 months) plus 30 days

This composite endpoint measured the safety and tolerability profile of idelalisib. "Clinically meaningful" abnormalities in vital signs and electrocardiograms (ECG) were as determined by the investigator.

Any AE
GroupValue95% CI
Idelalisib123
AE leading to drug discontinuation
GroupValue95% CI
Idelalisib35
Serious AE
GroupValue95% CI
Idelalisib72
Vital signs abnormal - clinically meaningful
GroupValue95% CI
Idelalisib0
ECG abnormal - clinically meaningful
GroupValue95% CI
Idelalisib0
Grade 3 or 4 hemoglobin
GroupValue95% CI
Idelalisib2
Grade 3 or 4 neutrophils
GroupValue95% CI
Idelalisib35
Grade 3 or 4 platelets
GroupValue95% CI
Idelalisib9
Study Drug Exposure Secondary · Start of Treatment to End of Treatment (up to 81 months)

The average idelalisib exposure was summarized.

GroupValue95% CI
Idelalisib13.2± 15.08
Idelalisib Plasma Concentration Secondary · Predose and at 1.5 hours (± 5 minutes) postdose on Day 29
Predose
GroupValue95% CI
Idelalisib471.6± 486.53
Postdose
GroupValue95% CI
Idelalisib2187.7± 1050.76
PK Parameter: Cmax Secondary · Predose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Days 1 and 29

Cmax at Days 1 and 29 was analyzed. Cmax is defined as the maximum concentration of drug.

Cmax at Day 1
GroupValue95% CI
Idelalisib2647.5± 1084.99
Cmax at Day 29
GroupValue95% CI
Idelalisib2258.8± 809.61

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events: Start of Treatment to End of Treatment (up to 81 months) plus 30 days; All-Cause Mortality: Baseline to Last Long-Term Follow-Up Visit (up to maximum of 7 years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Idelalisib
Serious: 72/125 (58%)
Deaths: 64/125

Serious adverse events (107 terms)

ReactionSystemIdelalisib
PyrexiaGeneral disorders
PneumoniaInfections and infestations
DiarrhoeaGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
ColitisGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Acute kidney injuryRenal and urinary disorders
NeutropeniaBlood and lymphatic system disorders
Peripheral swellingGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Cardiac failureCardiac disorders
MelaenaGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Chest painGeneral disorders
Multiple organ dysfunction syndromeGeneral disorders
Cytomegalovirus colitisInfections and infestations
Device related infectionInfections and infestations
Perirectal abscessInfections and infestations
Pneumocystis jirovecii pneumoniaInfections and infestations
SepsisInfections and infestations
Septic shockInfections and infestations
Urinary tract infectionInfections and infestations
Other adverse events (50 terms — click to expand)

ReactionSystemIdelalisib
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
Upper respiratory tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
VomitingGastrointestinal disorders
Weight decreasedInvestigations
AnaemiaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
Night sweatsSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
Aspartate aminotransferase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
AstheniaGeneral disorders
Oedema peripheralGeneral disorders
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
ConstipationGastrointestinal disorders
ChillsGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
DizzinessNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
LeukopeniaBlood and lymphatic system disorders
PainGeneral disorders
Blood creatinine increasedInvestigations
Dry skinSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
HypertensionVascular disorders
StomatitisGastrointestinal disorders
Mucosal inflammationGeneral disorders
PneumoniaInfections and infestations

Most-reported serious reactions: Pyrexia, Pneumonia, Diarrhoea, Febrile neutropenia, Colitis, Dehydration, Acute kidney injury, Neutropenia.

Data from ClinicalTrials.gov NCT01282424 adverse events section.

Sponsor's own description

The primary objective will be to assess the overall response rate and to evaluate the efficacy and safety of idelalisib (IDELA; GS-1101) in participants with previously treated indolent Non-Hodgkin Lymphoma (iNHL) that is refractory both to rituximab and to alkylating-agent-containing chemotherapy. Eligible participants will initiate oral therapy with idelalisib at a starting dose of 150 mg taken twice per day. Treatment with idelalisib can continue in compliant participants as long as the study is still ongoing and the participants appear to be benefiting from treatment with acceptable safety.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma.
    Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, et al · · 2014 · cited 810× · PMID 24450858 · DOI 10.1056/nejmoa1314583
  2. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
    Jiang N, Dai Q, Su X, Fu J, et al · · 2020 · cited 419× · PMID 32333246 · DOI 10.1007/s11033-020-05435-1
  3. Management of adverse events associated with idelalisib treatment: expert panel opinion.
    Coutré SE, Barrientos JC, Brown JR, de Vos S, et al · · 2015 · cited 236× · PMID 25726955 · DOI 10.3109/10428194.2015.1022770
  4. PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects.
    Mishra R, Patel H, Alanazi S, Kilroy MK, et al · · 2021 · cited 207× · PMID 33801659 · DOI 10.3390/ijms22073464
  5. Idelalisib, a selective inhibitor of phosphatidylinositol 3-kinase-δ, as therapy for previously treated indolent non-Hodgkin lymphoma.
    Flinn IW, Kahl BS, Leonard JP, Furman RR, et al · · 2014 · cited 164× · PMID 24615776 · DOI 10.1182/blood-2013-11-538546
  6. The present and future of PI3K inhibitors for cancer therapy.
    Castel P, Toska E, Engelman JA, Scaltriti M. · · 2021 · cited 152× · PMID 35118422 · DOI 10.1038/s43018-021-00218-4
  7. Advances in targeted therapy for malignant lymphoma.
    Wang L, Qin W, Huo YJ, Li X, et al · · 2020 · cited 88× · PMID 32296035 · DOI 10.1038/s41392-020-0113-2
  8. MicroRNA regulation of lymphocyte tolerance and autoimmunity.
    Simpson LJ, Ansel KM. · · 2015 · cited 70× · PMID 26030228 · DOI 10.1172/jci78090

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01282424.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing