Chronic Lymphocytic Leukemia (CLL) MedDRA version: 20.0 Level: PT Classification code 10008958 Term: Chronic lymphocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: GS-1101
Pharmaceutical Form: Tablet
CAS Number: 870281-82-6
Current Sponsor code: GS-1101
Concentration unit: mg milligram
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female =18 years of age. 2) Diagnosis of B-cell CLL, with diagnosis established according to IWCLL criteria [Hallek 2008] and documented within medical records. 3) CLL that warrants treatment (consistent with accepted criteria for initiation of therapy [Hallek 2008]). 4) Presence of radiographically measurable lymphadenopathy (defined as the presence of =1 nodal lesion that measures =2.0 cm in the longest dimension [LD] and =1.0 cm in the longest perpendicular dimension [LPD] as assessed by CT or MRI). 5) Prior treatment for CLL 6) In a subject whose last prior therapy contained an anti-CD20 antibody (eg, rituximab, ofatumumab, GA-101), evidence of disease improvement during that therapy or documentation of CLL progression =6 months after completion of that therapy. Note: Subjects who did not receive a therapeutic anti-CD20 antibody (eg, rituximab, ofatumumab, GA-101) as a component of the last prior therapy need not have experienced disease improvement or may have relapsed <6 months from the completion of the prior regimen. 7) Documentation of CLL progression <24 months since the completion of the last prior therapy for CLL. 8) Discontinuation of all therapy (including radiotherapy, chemotherapy, immunotherapy, systemic corticosteroids, or investigational therapy) for the treatment of CLL =3 weeks before randomization. 9) All acute toxic effects of any prior antitumor therapy resolved to Grade =1 before randomization (with the exception of alopecia [Grade 1 or 2 permitted], neurotoxicity [Grade 1 or 2 permitted], or bone marrow parameters [Grades 1, 2, 3, or 4 permitted). 10) Karnofsky performance score of =40. 11) Appropriate for non-cytotoxic-containing therapy. 12) Required baseline laboratory data (within 4 weeks prior to randomization) as shown in the table below. Note: Confirmation should be considered for out-of-range values to determine if the abnormality is real or artifactual. Values should be obtained within the screening period and should generally be the most recent measurement obtained. Subjects with any degree of neutropenia, thrombocytopenia, or anemia due to CLL or prior therapy may enroll. 13) For female subjects of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the screening visit (Visit 1) throughout the study treatment period and for 30 days following the last dose of study drug. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, has medically documented ovarian failure (with serum estradiol and folliclestimulating hormone [FSH] levels within the institutional postmenopausal range and a negative serum or urine ßHCG), or is menopausal (age =55 yea
Exclusion criteria
Exclusion criteria: 1) Known histological transformation from CLL to an aggressive lymphoma (ie, Richter transformation). Note: Biopsy documentation of the absence or presence of transformation is not required. 2) Presence of intermediate- or high-grade myelodysplastic syndrome (ie, subjects are excluded who have =5 bone marrow blasts; karotypic abnormalities other than normal, Y deletion, 5q deletion, or 20q deletion; or =2 lineages of cytopenias) [Greenberg 1997]. 3) History of a non-CLL malignancy except for the following: 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 randomization, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for =5 years. 4) Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of initiation of randomization (Visit 2). Note: Subjects with localized fungal infections of skin or nails are eligible. Subjects may be receiving prophylactic antiviral or antibacterial therapies at the discretion of the investigator; anti-pneumocystis prophylaxis is encouraged. For subjects who are at substantial risk of an infection (eg, influenza) that may be prevented by immunization, consideration should be given to providing the vaccine prior to initiation of protocol therapy. 5) Known history of drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension. 6) Known history of drug-induced pneumonitis. 7) Ongoing inflammatory bowel disease. 8) Ongoing alcohol or drug addiction. 9) Pregnancy or breastfeeding. 10) History of prior allogeneic bone marrow progenitor cell or solid organ transplantation. 11) Ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of CLL. Note: Subjects may use topical, enteric, or inhaled corticosteroids as therapy for comorbid conditions and systemic steroids for autoimmune anemia and/or thrombocytopenia. Ongoing use of low-dose systemic corticosteroids (=5 mg/day of methylprednisolone or equivalent) for rheumatologic conditions is permitted. During study participation, subjects may receive systemic or other corticosteroids as pretreatment for rituximab infusions or as needed for treatment-emergent comorbid conditions. 12) Prior therapy with any inhibitor of Bruton tyrosine kinase (BTK), Janus kinase (JAK), mammalian target of rapamycin (mTO
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of the addition of GS-1101 to rituximab on PFS in subjects with previously treated CLL ; Secondary Objective: • To determine the effect of the addition of GS-1101 to rituximab on the onset, magnitude, and duration of tumor control • To assess the effect of the addition of GS-1101 to rituximab on measures of subject wellbeing, including OS, HRQL, and performance status • To assess the effects of the addition of GS-1101 to rituximab on disease-associated biomarkers and to evaluate potential mechanisms of resistance to GS-1101 • To characterize exposure to study treatment as determined by treatment administration with each of the therapeutic agents, evaluation of GS-1101 plasma concentrations over time • To describe the safety profile observed with the addition of GS-1101 to rituximab • To estimate health resource utilization associated with the addition of GS-1101 to rituximab ; Primary end point(s): Progression-free survival (PFS) – 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 is CLL progression based on standard criteria and occurring for any reason (ie, increasing lymphadenopathy, organomegaly or bone marrow involvement; decreasing platelet count, hemoglobin, or neutrophil count; or worsening of disease-related symptoms) other than lymphocytosis alone ;Timepoint(s) of evaluation of this end point: every 8-12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall response rate (ORR) – defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR) • Time to response (TTR) – defined as the interval from randomization to the first documentation of CR or PR • Duration of response (DOR) – defined as the interval from the first documentation of CR or PR to the earlier of the first documentation of definitive disease progression or death from any cause • Time to treatment failure (TTF) – defined as the interval from randomization to the earliest of the first documentation of definitive disease progression, the permanent cessation of study drug (GS-1101/placebo) due to an adverse event, or death from any cause Percent change in lymph node area – defined as the percent change from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lymph nodes • Lymph node response rate – defined as the proportion of subjects who achieve a =50% decrease in the SPD of index lymph nodes • Splenomegaly response rate – defined as the proportion of subjects with baseline splenomegaly who achieve an on-study normalization or a decrease by =50% from baseline in the pretreatment enlargement of the splenic longest vertical dimension (LVD) (by imaging) or in the pretreatment enlargement of the splenic LVD below the left costal margin (by palpation) • Hepatomegaly response rate – defined as the proportion of subjects with baseline hepatomegaly who achieve an on-study normalization or a decrease by =50% from baseline in the pretreatment enlargement of the hepatic LVD (by imaging) or in t | — |
Countries
France, Germany, Italy, United Kingdom, United States
Contacts
Public ContactMedical Monitor
Gilead Sciences Inc.
Outcome results
None listed