Adults with relapsed or refractory chronic lymphocytic leukemia (CLL) MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Gazyvaro 1000 mg concentrate for solution for infusion
Product Name: Gazyvaro
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: OBINUTUZUMAB
CAS Number: 94914
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Documentation of relapsed or refractory CLL 2) Have an indication for treatment per modified IWCLL 2008 criteria; subjects without radiographically measureable disease (defined as = 1 lesion > 1.5cm in diameter as assessed by CT or MRI) must have bone marrow evaluation at screening 3) Adequate hematologic function as indicated by a platelet count = 50 x 10^9/L, a neutrophil count = 1 x 10^9/L and a hemoglobin = 8g/dL unless lower values are directly attributable to documented bone marrow burden of CLL 4) Adequate renal function as indicated by a CrCl = 50 mL/min calculated by the modified Cockroft-Gault formula or from a 24 hour urine collection 5) Adequate liver function as indicated by total bilirubin = 1.5x institutional upper limit of normal (ULN) unless attributed to Gilbert’s syndrome and AST/ALT = 2.5xULN 6) Male or female = 18 years of age 7) Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) = 2 8) Absence of active HBV infection (serological testing within 6 weeks prior to randomization or enrollment with the following results: HBsAg negative AND anti-HBcAb negative, or if anti-HBcAb positive, HBV DNA PCR negative) 9) HCV Ab negative or if Ab positive, negative HCV RNA PCR within 6 weeks prior to randomization or enrollment 10) Negative testing for HIV within 6 weeks prior to randomization or enrollment 11) Satisfies the following criteria: a) For female subjects of childbearing potential, willingness to abstain from sexual intercourse or use a protocol-specified method of contraception b) Male subjects of reproductive potential who engage in sexual intercourse must agree to use protocol-specified method(s) of contraception 12) Ability and willingness to provide written informed consent and adhere to protocol requirements including study visit schedule, drug administration plan, imaging studies, laboratory testing, other study procedures and restrictions including mandatory prophylaxis for Pneumocystis jirovecii pneumonia (PJP) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1) Known transformation of CLL (ie, Richter’s transformation, prolymphocytic leukemia) 2) Known CNS involvement 3) Progression on treatment with any inhibitor of BTK, SYK, PI3K, BCL-2 or obinutuzumab. The treatment and disease response history of subjects 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 4) Any treatment for CLL other than corticosteroids for symptomatic management within 28 days of the start of study treatment 5) Participation on a concurrent therapeutic clinical trial unless all treatment is complete with only ongoing surveillance 6) Diagnosis of or concern for progressive multifocal leukoencephalopathy 7) 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. 8) Active infection requiring systemic therapy 9) 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) 10) Active autoimmune disease including autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura requiring a higher corticosteroid equivalent than prednisone 10 mg daily. Higher doses of corticosteroids prescribed for any indication must be stopped >14 days prior to randomization or enrollment; exceptions may be made for corticosteroids prescribed specifically for management of CLL symptoms after discussion with the study medical monitor. 11) Diagnosis of inflammatory bowel disease or ongoing symptomatic pneumonitis 12) Ongoing CMV infection, treatment or prophylaxis for CMV within the past 28 days 13) History of stroke or intracranial hemorrhage within 12 months of randomization or enrollment; subjects requiring therapeutic anticoagulation for any indication should be discussed with the GCLLSG coordinating physician and/or medical monitor prior to screening 14) Legal incapacity, prisoners or subjects institutionalized by regulatory or court order, or any individual in dependence to study sponsor or any investigator 15) 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 16) Demonstration of QTc interval > 450 milliseconds or requirement for ongoing treatment with concomitant medications that prolong the QT interval 17) Known hypersensitivity to obinutuzumab, idelalisib or tirabrutinib or any of the excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the preliminary efficacy of the combination of tirabrutinib and idelalisib with obinutuzumab in subjects with relapsed or refractory CLL;Secondary Objective: The secondary objective of this study is to evaluate the safety and tolerability of the combination of tirabrutinib and idelalisib with and without obinutuzumab;Primary end point(s): The primary endpoint is the rate of complete remission (CR) per modified International Workshop on CLL (IWCLL) 2008 criteria at Week 25;Timepoint(s) of evaluation of this end point: Clinical/Laboratory visits will occur on Day 1, Week 1 to Week 5, then every 2 weeks until Week 25, then at Week 29, then every 12 weeks until Week 104. Qualitative treatment response assessment based on physical exam, laboratory parameters and presence of B-symptoms will be performed every 4 weeks until Week 33 Day 1 and then at all scheduled visits thereafter. Assessment of response per modified IWCLL 2008 criteria should also be recorded at the completion of 24 weeks on treatment and subsequent to any CT and/or bone marrow biopsy that is repeated while on study. Peripheral blood MRD will be assessed at on Day 1 of Weeks 1, 13, 25, 37, 49, 104, and EOT. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are: - Rate of complete response (CR) with bone marrow minimal residual disease (MRD) negativity (CR/BM MRD-) at Week 25 - Rate of CR with MRD negativity (<10-4) in peripheral blood (CR/PB MRD-) at Week 25 - Overall response Rate (ORR) at Week 25 including those subjects with a CR, CR with incomplete bone marrow recovery (CRi), partial remission (PR), and PR with lymphocytosis - Type, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs);Timepoint(s) of evaluation of this end point: Clinical/Laboratory visits will occur on Day 1 Week 1 to Week 5, then every 2 weeks until Week 25, then at Week 29, then every 12 weeks until Week 104. Qualitative treatment response assessment based on physical exam, laboratory parameters and presence of B-symptoms will be performed every 4 weeks until Week 33 Day 1 and then at all scheduled visits thereafter. Assessment of response per modified IWCLL 2008 criteria should also be recorded at the completion of 24 weeks on treatment and subsequent to any CT and/or bone marrow biopsy that is repeated while on study. Peripheral blood MRD will be assessed at on Day 1 of Weeks 1, 13, 25, 37, 49, 104, and EOT. AEs will be assessed at each visit. | — |
Countries
Germany
Contacts
Public ContactClinical Trials Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed