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LymphomaPhase 1NCT03834584

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

A Phase 1 study testing AG-636 in people with Lymphoma, run by Agios Pharmaceuticals, Inc. at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma
What is being tested?
AG-636
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
6 sitesUnited States
Study dates
24 May 2019to 17 Jun 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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 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.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Yale Cancer Center

    New Haven, Connecticut, 06519

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Weill Cornell Medical Center

    New York, New York, 10065

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 1 Study of AG-636 in the Treatment of Subjects With Advanced Lymphoma

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.

Read the 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]).

Conditions
Lymphoma
Being tested
AG-636
Keywords
Lymphoma, DHODH, Hodgkins Lymphoma, Non-Hodgkins Lymphoma, T-Cell Lymphoma
Medical subject headings
Lymphoma, Hodgkin Disease, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AG-636Drug

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

Study groups in NCT03834584
Study groupRoleWhat they receive
AG-636ExperimentalAG-636 dosed orally.
Receives: Drug: AG-636

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 28 days, on average

Secondary outcomes (4)

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

    As determined by the number of treatment-related Adverse Events and Serious Adverse Events

    Measured: Up to 24 weeks, on average

  2. Characterize the Pharmacodynamics of AG-636

    Measured by changes from baseline in circulating upstream metabolites

    Measured: Up to 24 weeks, on average

  3. Pharmacokinetics of AG-636 in plasma

    Determined by the plasma concentration versus time profile of AG-636

    Measured: Up to 24 weeks, on average

  4. Clinical activity of AG-636 in Lymphoma

    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)

    Measured: Up to 24 weeks, on average

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2019
  2. Study start24 May 2019
  3. Primary completion17 Jun 2020
  4. Study completion17 Jun 2020

Why it stopped: Terminated due to sponsor decision.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03834584
Sponsor's protocol ID
AG636-C-001
Status last verified
Aug 2020
First submitted
6 Feb 2019
Last updated
25 Aug 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AG-636 in people with Lymphoma, run by Agios Pharmaceuticals, Inc. at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Terminated due to sponsor decision.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03834584.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2020.

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