A Phase 1b Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of GS-9820 Monotherapy and Combination Therapy in Subjects with Lymphoid Malignancies
- Conditions
- on-Hodgkin's Lymphoma, Chronic Lymphocytic Leukemia, indolent Hodgkin's LymphomaB-cell related malignancyLymphoma10025319
- Registration Number
- NL-OMON39586
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 40
1) Male or female *18 years of age.
2) Diagnosis of B-cell iNHL, DLBCL, MCL, HL, or CLL as documented by medical records and with histology based on criteria established by the World Health Organization.
3) Prior treatment for lymphoid malignancy.
4) Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of *1 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) Discontinuation of all therapy (including radiotherapy, chemotherapy, immunotherapy, systemic corticosteroids, or investigational therapy) for the treatment of cancer *3 weeks before
the start of study therapy.
6) All acute toxic effects of any prior antitumor therapy resolved to Grade *1 before the start of study therapy (with the exception of alopecia [Grade 1 or 2 permitted], neurotoxicity [Grade 1 or 2
permitted], or bone marrow parameters [any of Grade 1, 2, or 3 permitted).
7) Karnofsky performance score of *60.
8) Required baseline laboratory data (within 4 weeks prior to start of study therapy) as shown in the table below.
9) 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 GS-9820.
10) For male subjects of childbearing potential having intercourse with females of childbearing potential, willingness to abstain from heterosexual intercourse or use a protocol-recommended method of contraception from the start of study therapy (Visit 2) throughout the study treatment period and for 90 days following the last dose of GS-9820 and to refrain from sperm donation from the start of study treatment (Visit 2) throughout the study treatment period and for 90
days following the last dose of GS-9820.
11) In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject*s cancer.
12) Willingness to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions.
13) Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, possible side effects,
potential risks and discomforts, and other pertinent aspects of study participation.
1) Known histological transformation to an aggressive form of NHL (ie, Richter transformation).
2) Known active central nervous system or leptomeningeal lymphoma.
3) 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).
4) History of a non-lymphoid 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 start of study therapy, 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.
5) Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of start of study therapy (Visit 2).
6) Ongoing liver injury, chronic active HCV, HBV, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
7) Ongoing drug-induced pneumonitis.
8) Ongoing inflammatory bowel disease.
9) Ongoing alcohol or drug addiction.
10) Pregnancy or breastfeeding.
11) History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
12) History of prior therapy with any inhibitor of AKT, Bruton tyrosine kinase (BTK), Janus kinase (JAK), mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K) (including GS-1101), or spleen tyrosine kinase (SYK).
13) Ongoing immunosuppressive therapy, including systemic corticosteroids for treatment of lymphoid malignancy. 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 lowdose 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.
14) Concurrent participation in another therapeutic clinical trial.
15) Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator*s opinion, could adversely affect the safety of the subject or impair the assessment of
study results.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To determine the MTD within the tested GS-9820 dose range and regimens</p><br>
- Secondary Outcome Measures
Name Time Method