A Study of AG-636 in the Treatment of Subjects With Advanced Lymphoma

NCT03834584 | Terminated Phase 1 FDA Drug

• 1 other identifier: AG636-C-001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 6

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.

Conditions

Lymphoma

Keywords

Lymphoma; DHODH; Hodgkins Lymphoma; Non-Hodgkins Lymphoma; T-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• The frequency of dose limiting toxicities (DLTs) associated with AG-636 administration during the first cycle (first 28 days) of treatment.

  Up to 28 days, on average

Secondary Outcomes (4)

• Characterize the Safety and Tolerability of AG-636 (number of treatment-related Adverse Events and Serious Adverse Events)

  Up to 24 weeks, on average

• Characterize the Pharmacodynamics of AG-636

  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

Study Arms (1)

AG-636

EXPERIMENTAL

AG-636 dosed orally.

Drug: AG-636

Interventions

AG-636 DRUG

AG-636 will be administered orally intermittently in 28-day cycles.

AG-636

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 ≤2.
• Have an absolute neutrophil count (ANC) ≥1,000/uL.
• Have a platelet count ≥75,000/uL.
• Have a serum total bilirubin level ≤1.5×ULN (upper limit of normal) in the absence of Gilbert syndrome. Subjects with Gilbert syndrome must have a serum total bilirubin level ≤1.5× their baseline value.
• Have alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤3.0×ULN, unless due to underlying hematologic malignancy. If ALT/AST elevations are determined to be due to involvement by the underlying hematologic malignancy, subjects must have ALT/AST levels \<5.0× the ULN.(Note: There are no specific requirements for alkaline phosphatase \[ALP\].)
• Have a creatinine clearance (CrCl) ≥ 30 mL/min (either measured or estimated by the Cockcroft-Gault formula). (Cockcroft-Gault formula for estimated creatinine clearance \[eCrCl\]: eCrCl = \[140 - Age\] × Weight \[kg\] × \[0.85 if Female\] / \[72 × serum creatinine (mg/dL)\]).
• Be fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy. Residual chronic toxicities of prior therapy, eg, alopecia, Grade ≤2 peripheral neuropathy, are allowed.

You may not qualify if:

• 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 \>1.
• Are unable to abstain from food or liquids other than water for 2 hours before and 2 hours after each dose of AG-636.
• 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.
• Acute myocardial infarction or angina pectoris.
• Stroke.
• Uncontrolled cardiac arrhythmia (subjects with rate-controlled atrial fibrillation are not excluded).
• Have any other concurrent severe and/or uncontrolled concomitant medical condition that could compromise participation in the study (eg, clinically significant pulmonary disease, clinically significant neurologic disorder).
• Have received any systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of AG-636.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (6)

Yale Cancer Center

New Haven, Connecticut, 06519, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 8, 2019
• Study Start: May 24, 2019
• Primary Completion: June 17, 2020
• Study Completion: June 17, 2020
• Last Updated: August 25, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)