A Phase 1 Study of AG-636 in the Treatment of Subjects With Advanced Lymphoma
Overview
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Agios Pharmaceuticals, Inc.
- Enrollment
- 11
- Locations
- 6
- Primary Endpoint
- The frequency of dose limiting toxicities (DLTs) associated with AG-636 administration during the first cycle (first 28 days) of treatment.
Overview
Brief Summary
This study will evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of AG-636, an oral Dihydroorotate Dehydrogenase (DHODH) inhibitor, in subjects with advanced lymphoma.
Detailed Description
The purpose of this Phase 1, multicenter, open-label study is to determine the maximum tolerated dose (MTD) of AG-636 and characterize its dose-limiting toxicities (DLTs) when given by mouth to subjects with advanced lymphoma that is refractory to standard treatment. During the dose escalation part of the study successive cohorts of subjects will be treated with increasing doses of AG-636 in order to determine its maximum tolerated dose (MTD). Subsequently, in the dose expansion part of the study, additional subjects will be treated at the MTD in order to confirm that dose's safety, tolerability, PK and PD, and to provide an opportunity to detect anti-lymphoma activity. The dose expansion part of the study will support the selection of a dose for future clinical studies (a recommended Phase 2 dose [RP2D]).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Be ≥18 years of age.
- •Have a pathologically confirmed diagnosis of a non-Hodgkin or Hodgkin lymphoma that has progressed in spite of prior treatment, and for whom additional effective (curative or life-prolonging) standard therapy is not available. The lymphomas included in this study must fall within one of the following 2017 World Health Organization categories:
- •Mature B-cell neoplasms (excluding plasma cell neoplasms, heavy chain disease, and primary central nervous system \[CNS\] lymphoma)
- •Mature T- and NK-cell neoplasms
- •Hodgkin lymphomas
- •Immunodeficiency-associated lymphoproliferative disorders
- •In the case of subjects who have lymphoma for which high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) is considered a standard curative therapy, eligibility for this study requires that the subject's disease has relapsed after HD-ASCT, that the subject is not eligible for HD-ASCT, or that the subject has refused HD-ASCT.
- •Have disease that can be clinically evaluated for improvement or progression. In the dose expansion phase of the study, subjects must have disease that is measurable (as defined by either the Lugano criteria for lymphoma or the 2011 ISCL/USCLC/EORTC criteria for MF/SS).
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Have an absolute neutrophil count (ANC) ≥1,000/uL.
Exclusion Criteria
- •Have a primary central nervous system (CNS) lymphoma.
- •Have lymphomatous involvement of the CNS that is symptomatic or requires therapy. However, subjects who have completed treatment for lymphoma involving the CNS and have no further evidence of disease in the CNS may be enrolled in this study.
- •Have lymphoma that requires immediate cytoreductive therapy.
- •Have low-grade lymphoma that does not meet conventional criteria for requiring treatment.
- •Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of AG-636, including any unresolved nausea, vomiting, or diarrhea that is National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade \>
- •Are unable to abstain from food or liquids other than water for 2 hours before and 2 hours after each dose of AG-
- •Have an active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
- •Have an active infection (bacterial, viral, or fungal) that cannot be controlled with treatment.
- •Have had significant active cardiac disease within 6 months prior to the start of study treatment, including any of the following:
- •New York Heart Association (NYHA) class III or IV congestive heart failure.
Arms & Interventions
AG-636
AG-636 dosed orally.
Intervention: AG-636 (Drug)
Outcomes
Primary Outcomes
The frequency of dose limiting toxicities (DLTs) associated with AG-636 administration during the first cycle (first 28 days) of treatment.
Time Frame: Up to 28 days, on average
Secondary Outcomes
- Characterize the Pharmacodynamics of AG-636(Up to 24 weeks, on average)
- Characterize the Safety and Tolerability of AG-636 (number of treatment-related Adverse Events and Serious Adverse Events)(Up to 24 weeks, on average)
- Pharmacokinetics of AG-636 in plasma(Up to 24 weeks, on average)
- Clinical activity of AG-636 in Lymphoma(Up to 24 weeks, on average)