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Clinical Trial 20054

Cancer Type: Malignant Hematology
Interventions:AG-636

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Bijal Shah

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

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

Summary

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]).

Objective

Primary Objective: To determine the maximum tolerated dose (MTD) of AG-636 and characterize its dose-limiting toxicities (DLTs) when given to subjects with advanced lymphoma Secondary Objectives: To characterize the safety and tolerability of AG-636 To characterize the pharmacokinetics (PK) of AG-636 and its metabolite AGI-0045653 in plasma To characterize the pharmacodynamics (PD) of AG-636 by assessing plasma concentrations of DHO To characterize any anti-lymphoma activity that may be associated with AG-636 treatment

Inclusion Criteria

  • 18 years of age or older
  • 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 participants 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 participant's disease has relapsed after HD-ASCT, that the participant is not eligible for HD-ASCT, or that the participant has refused HD-ASCT.
  • Have disease that can be clinically evaluated for improvement or progression. In the dose expansion phase of the study, participants 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).
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
  • Lab values as outlined per protocol
  • Be fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy. Residual chronic toxicities of prior therapy, e.g., 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.

  • Exclusion Criteria

  • Primary central nervous system (CNS) lymphoma.
  • Lymphomatous involvement of the CNS that is symptomatic or requires therapy. However, participants 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.
  • Lymphoma that requires immediate cytoreductive therapy.
  • Low-grade lymphoma that does not meet conventional criteria for requiring treatment.
  • 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.
  • Unable to abstain from food or liquids other than water for 2 hours before and 2 hours after each dose of AG-636.
  • Active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
  • Active infection (bacterial, viral, or fungal) that cannot be controlled with treatment.
  • Significant active cardiac disease within 6 months prior to the start of study treatment, as defined per protocol.
  • Heart rate-corrected QT interval using Fridericia's method (QTcF) >470 msec. Participants with bundle branch block and a QTcF >470 msec should be discussed with the Medical Monitor for potential inclusion.
  • 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).
  • Received any systemic anticancer treatment or radiotherapy less than 2 weeks before the first dose of AG-636.
  • Received radioimmunotherapy less than 6 weeks before the first dose of AG-636.
  • Received treatment with an investigational small molecule > Taking medications that are sensitive substrates of CYP2C8, and that cannot be discontinued prior to starting treatment with AG-636.
  • 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.
  • Pregnant or breastfeeding.
  • Any other medical or psychological condition deemed by the Investigator to be likely to interfere with the participant's ability to give informed consent or participate in the study.
  • Has concurrent malignancy other than lymphoma; participants must have been free of other malignancies for ≥1 year before the start of study treatment. However, participants with the following history/concurrent conditions are allowed: (a) Basal or squamous cell carcinoma of the skin, (b) Carcinoma in situ of the cervix (c) Carcinoma in situ of the breast (d) Incidental histologic finding of prostate cancer.