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Safety and Efficacy of the Combination of Tirabrutinib and Idelalisib With and Without Obinutuzumab in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02968563
Recruitment Status : Active, not recruiting
First Posted : November 18, 2016
Last Update Posted : January 18, 2019
Sponsor:
Collaborator:
German CLL Study Group
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:

The primary objective of this study is to determine the preliminary efficacy and safety of the combination of tirabrutinib and idelalisib with obinutuzumab in adults with relapsed or refractory chronic lymphocytic leukemia (CLL).

The study has a 6 patient per arm safety run-in to evaluate safety prior to the enrollment of subsequent participants. The primary objective is evaluation of efficacy with the secondary objective evaluation of safety and evaluation of additional parameters of efficacy. The treatment period is adaptive, with a duration of active treatment up to two years and a total follow-up on study of 5 years for time-dependent outcome variables.


Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Tirabrutinib Drug: Idelalisib Drug: Obinutuzumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: With Amendment 3, randomization will be discontinued. All subsequently enrolled participants will enter Arm B (tirabrutinib + idelalisib + obinutuzumab).
Primary Purpose: Treatment
Official Title: A Prospective, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib (GS-4059) and Idelalisib With and Without Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia
Actual Study Start Date : December 13, 2016
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : February 2024


Arm Intervention/treatment
Experimental: Tirabrutinib + idelalisib (Arm A)
Participants will receive tirabrutinib and idelalisib for up to 104 weeks.
Drug: Tirabrutinib
Capsules or tablets administered orally once daily
Other Name: GS-4059

Drug: Idelalisib
Tablets administered orally once daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101

Experimental: Tirabrutinib + idelalisib + obinutuzumab (Arm B)
Participants will receive obinutuzumab over 21 weeks and the combination of tirabrutinib and idelalisib for up to 104 weeks.
Drug: Tirabrutinib
Capsules or tablets administered orally once daily
Other Name: GS-4059

Drug: Idelalisib
Tablets administered orally once daily
Other Names:
  • Zydelig®
  • GS-1101
  • CAL-101

Drug: Obinutuzumab
1000 mg/40 mL single-use vials administered intravenously for a total of 8 doses over 21 weeks
Other Names:
  • Gazyvaro®
  • Gazyva®
  • GA101




Primary Outcome Measures :
  1. Rate of Complete Remission (CR) as Assessed by the Investigator Using the Modified International Workshop on CLL (IWCLL) 2008 criteria [ Time Frame: After the completion of 24 weeks of treatment ]

Secondary Outcome Measures :
  1. Rate of CR with Bone Marrow Minimal Residual Disease (MRD) Negativity [ Time Frame: After the completion of 24 weeks of treatment ]
  2. Rate of CR with Peripheral Blood MRD Negativity [ Time Frame: After the completion of 24 weeks of treatment ]
  3. Overall Response Rate (ORR) [ Time Frame: After the completion of 24 weeks of treatment ]
  4. Duration of Response (DOR) [ Time Frame: After the completion of 24 weeks of treatment ]
  5. Progression-Free Survival [ Time Frame: Up to 5 years ]
  6. Overall Safety as Assessed by the Frequency of Treatment-Emergent Adverse Events (AE) and Treatment-Emergent Serious AEs [ Time Frame: Up to 5 years ]


Information from the National Library of Medicine

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

Key Inclusion Criteria:

  • Documentation of relapsed or refractory CLL
  • Requiring treatment per modified IWCLL 2008 criteria; subjects without radiographically mensurable disease (defined as ≥ 1 lesion > 1.5 cm in diameter as assessed by computed tomography (CT) or magnetic resonance imaging [MRI]) must have bone marrow evaluation at screening
  • Adequate hematologic function: platelet count ≥ 50 × 10^9/L, neutrophil count ≥ 1 × 10^9/L, hemoglobin ≥ 8 g/dL unless lower values are directly attributable to documented bone marrow burden of CLL
  • Creatinine clearance (CrCl) ≥ 50 mL/min
  • Total bilirubin ≤ 1.5× institutional upper limit of normal (ULN) unless attributed to Gilbert's syndrome and aspartate transaminase (AST)/alanine transaminase (ALT) ≤ 2.5×ULN
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 2
  • Absence of active HIV, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, and cytomegalovirus (CMV) infection
  • Satisfies the following criteria:

    • For females of childbearing potential, willingness to abstain from sexual intercourse or use a protocol-specified method of contraception as described in the study protocol
    • Males of reproductive potential who engage in sexual intercourse must agree to use protocol-specified method(s) of contraception as described in the study protocol
  • Able to comply with study procedures and restrictions including mandatory prophylaxis for Pneumocystis jirovecii pneumonia (PJP)

Key Exclusion Criteria:

  • Known transformation of CLL (ie, Richter's transformation, prolymphocytic leukemia)
  • Known central nervous system (CNS) involvement
  • Progression on treatment with any inhibitor of Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (BCL-2), or obinutuzumab. The treatment and disease response history of individuals with prior treatment with agents in these classes should be reviewed by the sponsor or the GCLLSG study office prior to enrollment to clarify sensitivity to these treatments.
  • Any treatment for CLL other than corticosteroids for symptomatic management within 28 days of the start of study treatment
  • Participation on a concurrent therapeutic clinical trial unless all treatment is complete with only ongoing surveillance
  • Diagnosis of or concern for progressive multifocal leukoencephalopathy
  • History of myelodysplastic syndrome or another malignancy other than CLL, except for the following: any malignancy that has been in complete remission for 3 years, 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 start of study therapy
  • Active infection requiring systemic therapy
  • Pregnant or nursing women (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment and monthly during therapy)
  • Active autoimmune disease or the need for higher than prednisone 10 mg daily unless for management of CLL symptoms
  • Treatment or prophylaxis for CMV within the past 28 days
  • History of stroke or intracranial hemorrhage within 12 months of randomization; subjects requiring therapeutic anticoagulation for any indication should be discussed with the German CLL Study Group (GCLLSG) cooperating physician and/or medical monitor prior to screening.
  • Use of a strong CYP3A4 or a strong P-gp inducer within 2 weeks of first dose of study treatment or anticipated chronic use while on study
  • Demonstration of corrected QT (QTc) interval > 450 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02968563


Locations
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Germany
Mutlangen, Baden-Wuerttemberg, Germany
Ravensburg, Baden-Wuerttemberg, Germany
Ulm, Baden-Württemberg, Germany
Augsburg, Bavaria, Germany
München, Bavaria, Germany
München, Bayern, Germany
Regensburg, Bayern, Germany
Frankfurt, Brandenburg, Germany
Gießen, Hessen, Germany
Koln, Nordrhein-Westfalen, Germany
Mönchengladbach, Nordrhein-Westfalen, Germany
Leipzig, Sachsen, Germany
Luebeck, Germany
Mannheim, Germany
Sponsors and Collaborators
Gilead Sciences
German CLL Study Group
Investigators
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Study Director: Gilead Study Director Gilead Sciences

Additional Information:
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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02968563     History of Changes
Other Study ID Numbers: GS-US-401-1958
2015-003909-42 ( EudraCT Number )
CLLRUmbrella1 ( Other Identifier: German CLL Study Group )
First Posted: November 18, 2016    Key Record Dates
Last Update Posted: January 18, 2019
Last Verified: January 2019

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Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Idelalisib
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
Obinutuzumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action