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Clinical Trial 20951

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT04603001

Phase: Phase I
Principal Investigator: Sweet, Kendra

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or 1-800-679-0775 Learn More
Overview

Study Title

A Phase 1 Study of Oral LY3410738 in Patients with Advanced Hematologic Malignancies with IDH1 or IDH2 Mutations

Summary

This is an open-label, multi-center Phase 1 study of LY3410738, an oral, covalent IDH inhibitor, in patients with IDH1 and/or IDH2-mutant advanced hematologic malignancies who have received standard therapy

Objective

Dose Escalation 1. To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of oral LY3410738 in patients with IDH1 or IDH2-mutant advanced hematologic malignancies; 2. To determine the safety and tolerability of LY3410738; 3. To characterize the pharmacokinetics (PK) properties of LY3410738; 4. To characterize the pharmacodynamic (PD) properties of LY3410738 as expressed by change in 2-hydroxyglutarate (2-HG) oncometabolite levels in plasma; 5. To assess the preliminary anti-tumor activity of LY3410738 based on investigator assessed response using modified 2017 European LeukemiaNet (ELN) recommendations for acute myeloid leukemia (AML) or modified International Working Group (IWG) Response Criteria in myelodysplastic syndrome (MDS), or other appropriate response criteria based on disease type (Appendix F). Dose Expansion 1. To assess the preliminary anti-tumor activity of LY3410738 based on overall response rate (ORR) using modified 2017 ELN recommendations for AML or modified IWG Response Criteria in MDS, or other appropriate response criteria based on disease type as assessed by the investigator; 2. To assess the preliminary anti-tumor activity of LY3410738 based on: - Best overall response (BOR); - CR Rate (CRR); - Rate of CR+ CR with partial hematologic recovery (CRh) for patients with AML; - Duration of response (DOR); - Time to remission/response (TTR); - Event free survival (EFS); - Overall survival (OS); - Red blood cell (RBC) transfusion independence (TI); - Platelet transfusion independence; - Hematologic improvement (HI) for patients with MDS (according to IWG criteria); - Rate of patients successfully bridged to transplant; 3. To determine the safety and tolerability of LY3410738; 4. To characterize the PK properties of LY3410738; 5. To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma.

Treatments

Therapies

Immunotherapy

Medications

LY3410738 ()

Inclusion Criteria

  • Advanced IDH mutant hematologic malignancy
  • Patients must have received prior therapy
  • Blasts at least 5% in bone marrow.
  • Patients must have a qualifying IDH1 R132, IDH2 R140 or IDH2 R172 mutation
  • Eastern Cooperative Oncology Group (ECOG) 0-2
  • Adequate organ function
  • Ability to swallow capsules or tablets
  • Ability to comply with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation
  • Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment.

  • Exclusion Criteria

  • Investigational agent or anticancer therapy within 2 weeks or 5 half-lives, whichever is shorter; or investigational monoclonal antibody within 4 weeks prior to planned start of LY3410738
  • Major surgery within 4 weeks prior to planned start of LY3410738.
  • Active, uncontrolled clinically significant systemic bacterial, viral, fungal or parasitic infection or an unexplained fever > 38.5ºC during screening or on the first day of study drug administration.
  • Another concurrent malignancy requiring active therapy.
  • Active central nervous system involvement
  • Any unresolved toxicities from prior therapy greater than CTCAE v5.0 Grade 2 at the time of starting study treatment except for alopecia.
  • History of hematopoietic stem cell transplant (HSCT) or CAR-T therapy within 60 days of the first dose of LY3410738
  • Clinically significant cardiovascular disease
  • Active hepatitis B virus (HBV)
  • Active hepatitis C virus (HCV)
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption of the study drug
  • Current treatment with certain strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers and/or P-gp inhibitor, with the exception of patients being treated with allowed antifungal inhibitors of CYP3A4
  • Treatment with proton pump inhibitor (PPIs) within 7 days of starting LY3410738
  • Any serious underlying medical or psychiatric condition (e.g. alcohol or drug abuse), dementia or altered mental status or any issue that would impair the ability of the patient to understand informed consent or that in the opinion of the investigator would contraindicate the patient's participation in the study or confound the results of the study
  • Known human immunodeficiency virus (HIV), excluded due to potential drug-drug interactions between anti-retroviral medications and LY3410738
  • Pregnancy, lactation or plan to breastfeeding during the study or within 90 days of the last dose of study intervention
  • Known hypersensitivity to any of the components of LY3410738 or its formulation

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