Entospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies

Browse trials for

• Leukemia, Lymphocytic, Chronic, B-Cell 1,648
• Lymphoma, Mantle-Cell 810
• Lymphoma, Large B-Cell, Diffuse 1,432
• Leukemia 5,475
• Lymphoma 5,623
• Waldenstrom Macroglobulinemia 372

Keywords

• GS-US-339-0103
• SYK inhibitor
• PI3K inhibitor
• GS-9973
• GS 9973
• GS-1101
• GS 1101
• Cal-101
• Cal 101
• idelalisib
• leukemia
• lymphoma
• CLL
• MCL
• DLBCL
• iNHL
• FL
• MZL
• LPL
• SLL
• WM
• Waldenström's macroglobulinemia

Leukemia, Lymphocytic, Chronic, B-Cell

1,648 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 245 are open to participants now.

This study's enrollment of 66 is above the median of 40 across 1,356 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.

Lead sponsor

Gilead Sciences is the lead sponsor of 689 studies on the registry; 24 are open to participants now.

Of its 261 completed or terminated interventional studies of FDA-regulated products, 251 (96%) have results posted.

Eligibility criteria

Study arms

• Experimental
  Entospletinib + idelalisib

  Entospletinib plus idelalisib at one of 4 dose combinations (400 mg/100 mg; 600 mg/100 mg; 800 mg/100 mg; 800 mg/150 mg). After discontinuation of entospletinib+idelalisib combination therapy, and following a washout period, participants may continue to receive entospletinib 400 mg monotherapy.

  Drug: Entospletinib · Drug: Idelalisib

Interventions

• DrugEntospletinib

  Entospletinib tablets administered orally twice daily

  Also known as: GS-9973

• DrugIdelalisib

  Idelalisib tablets administered orally twice daily

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

Primary outcomes

1. Objective Response Rate (ORR)

   ORR assessed by the Independent Review Committee (IRC), was based on the International Working Group Revised Response Criteria (Cheson, 2012) and investigator's response, defined as the percentage of participants achieving a complete response (CR) or partial response (PR) (or very good partial response \[VGPR\] or minor response \[MR\] for participants with LPL/WM). 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 the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but \< 50% decrease from baseline in serum monoclonal immunoglobulin M (IgM) concentration by serum protein electrophoresis (SPEP) respectively.

   Time frame: Start of treatment to end of treatment (Up to 18 months)

Secondary outcomes

1. Percentage of Participants Experiencing Treatment-Emergent Adverse Events

   A treatment-emergent Adverse Event (AE) was defined as any AE with an onset date of on or after the study drug start date and no later than 30 days after permanent discontinuation of study drugs or an AE leading to premature discontinuation of study drug. An AE is any untoward medical occurrence in a clinical investigation where participants administered a medicinal product, and which does not necessarily have a causal relationship with this treatment.

   Time frame: First dose date up to the last dose date plus 30 days (maximum duration: 19 months)

2. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

   A treatment-emergent laboratory (Hematology, Serum Chemistry and Urinalysis) abnormality was defined as an abnormality that, compared to baseline, worsens by ≥ 1 grade in the period from the first dose of study drug. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 0 = none, Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening or disabling. If baseline data are missing, then any graded abnormality (i.e., an abnormality that is Grade ≥ 1 in severity) will be considered treatment-emergent. The percentage of participants in each worst postbaseline grade is reported.

   Time frame: First dose date up to the last dose date plus 30 days (maximum: 18 months)

3. Maximum Tolerated Dose Level

   Maximum tolerated dose (MTD) is defined as the highest dose level that was consistently well tolerated without dose limiting toxicity (DLT) for the majority of participants time on treatment (ie,\> 50%) as determined by the investigator for each participant. DLTs are defined as Grade 4 hematological toxicities persisting for ≥ 14 days or Grade ≥ 3 toxicities of other types.

   Time frame: First dose (entospelinib + idelalisib) date up to 6 months

4. Progression-free Survival (PFS)

   PFS was defined as the interval from the first dose of study drug to the earlier of the first documentation of definitive disease progression or death from any cause.

   Time frame: Start of treatment to end of treatment (Up to 18 months)

5. Duration of Response (DOR)

   DOR was defined as the interval from the first-time response (CR or PR \[or VGPR or MR for participants with LPL/WM\]) is achieved to the earlier of the first documentation of definitive disease progression or death from any cause.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 the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but \< 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively.

   Time frame: Start of treatment to end of treatment (Up to 18 months)

6. Time to Response (TTR)

   TTR was defined as the interval from the first dose of entospletinib/idelalisib to the time response (CR or PR \[or VGPR or MR for participants with LPL/WM\]) is first achieved. 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 the longest perpendicular diameters of all index lesions, with no new lesions. VGPR and MR were defined as ≥ 90% and ≥ 25% but \< 50% decrease from baseline in serum monoclonal IgM concentration by SPEP respectively.

   Time frame: Start of treatment to end of treatment (Up to 18 months)

Baseline characteristics

Publications

• Barr PM, Saylors GB, Spurgeon SE, Cheson BD, Greenwald DR, O'Brien SM, Liem AK, Mclntyre RE, Joshi A, Abella-Dominicis E, Hawkins MJ, Reddy A, Di Paolo J, Lee H, He J, Hu J, Dreiling LK, Friedberg JW. Phase 2 study of idelalisib and entospletinib: pneumonitis limits combination therapy in relapsed refractory CLL and NHL. Blood. 2016 May 19;127(20):2411-5. doi: 10.1182/blood-2015-12-683516. Epub 2016 Mar 11. PubMed 26968534 ↗