A Study of AG-636 in the Treatment of Subjects With Advanced Lymphoma
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|ClinicalTrials.gov Identifier: NCT03834584|
Recruitment Status : Terminated (Terminated due to sponsor decision.)
First Posted : February 8, 2019
Last Update Posted : August 25, 2020
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|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: AG-636||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||11 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of AG-636 in the Treatment of Subjects With Advanced Lymphoma|
|Actual Study Start Date :||May 24, 2019|
|Actual Primary Completion Date :||June 17, 2020|
|Actual Study Completion Date :||June 17, 2020|
AG-636 dosed orally.
AG-636 will be administered orally intermittently in 28-day cycles.
- 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 ]
- Characterize the Safety and Tolerability of AG-636 (number of treatment-related Adverse Events and Serious Adverse Events) [ Time Frame: Up to 24 weeks, on average ]As determined by the number of treatment-related Adverse Events and Serious Adverse Events
- Characterize the Pharmacodynamics of AG-636 [ Time Frame: Up to 24 weeks, on average ]Measured by changes from baseline in circulating upstream metabolites
- Pharmacokinetics of AG-636 in plasma [ Time Frame: Up to 24 weeks, on average ]Determined by the plasma concentration versus time profile of AG-636
- Clinical activity of AG-636 in Lymphoma [ Time Frame: Up to 24 weeks, on average ]Assessed by either the Lugano criteria for lymphoma or the 2011 International Society for Cutaneous Lymphomas (ISCL)/United States Cutaneous Lymphoma Consortium (USCLC)/ European Organization for Research and Treatment of Cancer (EORTC) criteria for mycosis fungoides (MF)/Sézary syndrome (SS)
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- If female with reproductive potential, must have a negative serum pregnancy test prior to the start of study therapy. Females of reproductive potential, as well as fertile men and their female partners of reproductive potential, must agree to use 2 effective forms of contraception.
- Able to understand and have provided written informed consent.
- 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.
- Uncontrolled cardiac arrhythmia (subjects with rate-controlled atrial fibrillation are not excluded).
- Have a heart rate-corrected QT interval using Fridericia's method (QTcF) >470 msec. Patients with bundle branch block and a QTcF >470 msec should be discussed with the Medical Monitor for potential inclusion.
- 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.
- Have received radioimmunotherapy less than 6 weeks before the first dose of AG-636.
- Have received treatment with an investigational small molecule <2 weeks before the first dose of AG-636.
- Are taking medications that are sensitive substrates of CYP2C8, and that cannot be discontinued prior to starting treatment with AG-636.
- Are taking medications that are sensitive substrates of either P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP), and that cannot be discontinued prior to starting treatment with AG-636.
- Are pregnant or breastfeeding.
- Have any other medical or psychological condition deemed by the Investigator to be likely to interfere with the subject's ability to give informed consent or participate in the study.
Have concurrent malignancy other than lymphoma; subjects must have been free of other malignancies for ≥1 year before the start of study treatment. However, subjects with the following history/concurrent conditions are allowed:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03834584
|United States, Connecticut|
|Yale Cancer Center|
|New Haven, Connecticut, United States, 06519|
|United States, Florida|
|Moffitt Cancer Center|
|Tampa, Florida, United States, 33612|
|United States, Nebraska|
|University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Weill Cornell Medical Center|
|New York, New York, United States, 10065|
|United States, Washington|
|Seattle Cancer Care Alliance|
|Seattle, Washington, United States, 98109|
|Responsible Party:||Agios Pharmaceuticals, Inc.|
|Other Study ID Numbers:||
|First Posted:||February 8, 2019 Key Record Dates|
|Last Update Posted:||August 25, 2020|
|Last Verified:||August 2020|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms by Histologic Type
Immune System Diseases