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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04603001
Registration number
NCT04603001
Ethics application status
Date submitted
12/10/2020
Date registered
26/10/2020
Date last updated
5/06/2024
Titles & IDs
Public title
Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
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Scientific title
A Phase 1 Study of Oral LY3410738 in Patients With Advanced Hematologic Malignancies With IDH1 or IDH2 Mutations
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Secondary ID [1]
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2020-002830-33
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Secondary ID [2]
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LOXO-IDH-20001
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia (AML)
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Myelodysplastic Syndrome (MDS)
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Chronic Myelomonocytic Leukemia (CMML)
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Myeloproliferative Neoplasms (MPNs)
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Condition category
Condition code
Cancer
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Leukaemia - Acute leukaemia
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Children's - Leukaemia & Lymphoma
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Blood
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Haematological diseases
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Blood
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Other blood disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - LY3410738
Treatment: Drugs - Venetoclax
Treatment: Drugs - Azacitidine
Experimental: Dose Escalation Arm A (Monotherapy) - Patients not requiring a strong cytochrome P450 3A4 (CYP3A4) inhibitor.
Experimental: Dose Escalation Arm B (Monotherapy) - Patients requiring a strong CYP3A4 inhibitor for active management or prevention of a lifethreatening condition, such as an azole administered to prevent invasive fungal infection.
Experimental: Dose Escalation Arm C (LY3410738, Venetoclax, and Azacitidine) - Patients with no prior venetoclax therapy and not requiring a strong CYP3A4 inhibitor for active treatment within 7 days of starting LY3410738.
Experimental: Cohort 1 - Patients with relapsed/refractory (R/R) AML harboring an IDH1 R132 mutation who have received a prior IDH inhibitor.
Experimental: Cohort 2 - Patients with R/R AML harboring an IDH1 R132 mutation who have not received a prior IDH inhibitor.
Experimental: Cohort 3 - Patients with R/R MDS, chronic myelomonocytic leukemia (CMML) or other advanced hematologic malignancy harboring an IDH1 R132 mutation.
Experimental: Cohort 4 - Patients with R/R AML, MDS, CMML or other advanced hematologic malignancy harboring IDH2 mutations.
Experimental: Cohort 5 - Patients with newly diagnosed AML, R/R AML, or other advanced hematologic malignancy harboring IDH1 and/or IDH2 mutations with no prior venetoclax therapy. Strong CYP3A4 inhibitor allowed but not required.
Treatment: Drugs: LY3410738
Oral LY3410738
Treatment: Drugs: Venetoclax
Oral venetoclax
Treatment: Drugs: Azacitidine
Subcutaneous or intravenous azacitidine
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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To determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D)
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Assessment method [1]
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For Dose Escalation
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Timepoint [1]
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Up to 30 months
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Primary outcome [2]
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To assess the activity of LY3410738 as measured by the overall response rate (ORR) per the Investigator assessment
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Assessment method [2]
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For Dose Expansion
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Timepoint [2]
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Up to 30 months
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Secondary outcome [1]
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To determine the safety profile and tolerability of LY3410738 including acute and chronic toxicities by collecting and evaluating adverse events and treatment emergent adverse events
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Assessment method [1]
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For Dose Escalation
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Timepoint [1]
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Up to 30 months
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Secondary outcome [2]
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To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
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Assessment method [2]
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For Dose Escalation
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Timepoint [2]
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Up to 30 months
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Secondary outcome [3]
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To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma
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Assessment method [3]
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For Dose Escalation
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Timepoint [3]
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Up to 30 months
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Secondary outcome [4]
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To assess the activity of LY3410738 as measured by the overall response rate (ORR) per Investigator assessment
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Assessment method [4]
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For Dose Escalation
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Timepoint [4]
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Up to 30 months
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Secondary outcome [5]
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To assess the activity of LY3410738 as measured by Best Overall Response (BOR) per Investigator assessment
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Assessment method [5]
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For Dose Expansion
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Timepoint [5]
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Up to 30 months
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Secondary outcome [6]
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To assess the activity of LY3410738 by Complete Remission (CR) Rate (CRR) plus partial hematologic recovery (AML patients)
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Assessment method [6]
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For Dose Expansion
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Timepoint [6]
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Up to 30 months
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Secondary outcome [7]
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To assess the activity of LY3410738 by Duration of Response
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Assessment method [7]
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For Dose Expansion
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Timepoint [7]
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Up to 30 months
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Secondary outcome [8]
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To assess the activity of LY3410738 by Hematologic improvement in patients with MDS
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Assessment method [8]
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For Dose Expansion
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Timepoint [8]
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Up to 30 months
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Secondary outcome [9]
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To determine the safety profile and tolerability of LY3410738 including acute and chronic toxicities by collecting and evaluating Adverse events and treatment emergent adverse events
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Assessment method [9]
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For Dose Expansion
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Timepoint [9]
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Up to 30 months
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Secondary outcome [10]
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To characterize the pharmacokinetics (PK) properties of LY3410738 by collecting and evaluating serum at protocol specified time points
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Assessment method [10]
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For Dose Expansion
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Timepoint [10]
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Up to 30 months
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Secondary outcome [11]
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To characterize the pharmacodynamic properties of LY3410738 as expressed by change in 2-HG oncometabolite levels in plasma.
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Assessment method [11]
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For Dose Expansion
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Timepoint [11]
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Up to 30 months
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Eligibility
Key inclusion criteria
- Advanced IDH mutant hematologic malignancy including:
-- For Dose Escalation Arm C and Dose Expansion Cohort 5:
- Patients with newly diagnosed AML who are 75 years or older or have comorbidities
that preclude the use of intensive chemotherapy
- Patients with R/R AML (US only)
- 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 to 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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
- For Dose Escalation Arm C and Dose Expansion Cohort 5:
- Prior venetoclax treatment is not allowed.
- Patients are allowed to receive up to 1 cycle of single agent azacitidine or
azacitidine plus venetoclax while waiting for results of locally obtained
molecular profiling, including IDH1/IDH2 mutational status, prior to starting on
study.
- 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 chimeric antigen receptor
T-cell (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- glycoprotein (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 antiretroviral 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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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/12/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/05/2025
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Actual
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Sample size
Target
260
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
VIC,WA
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Recruitment hospital [1]
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Peter MacCallum Cancer Centre - Melbourne
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Recruitment hospital [2]
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The Alfred Hospital - Melbourne
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Recruitment hospital [3]
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Linear Clinical Research - Nedlands
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Recruitment postcode(s) [1]
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3000 - Melbourne
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Recruitment postcode(s) [2]
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3004 - Melbourne
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Recruitment postcode(s) [3]
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6009 - Nedlands
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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Country [2]
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United States of America
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State/province [2]
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Florida
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Country [3]
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United States of America
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State/province [3]
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Illinois
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Country [4]
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United States of America
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State/province [4]
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Massachusetts
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Country [5]
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United States of America
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State/province [5]
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New York
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Country [6]
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United States of America
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State/province [6]
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North Carolina
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Country [7]
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United States of America
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State/province [7]
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Tennessee
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Country [8]
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United States of America
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State/province [8]
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Texas
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Country [9]
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Belgium
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State/province [9]
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Brussels
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Country [10]
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Canada
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State/province [10]
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British Columbia
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Country [11]
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Canada
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State/province [11]
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Ontario
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Country [12]
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Canada
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State/province [12]
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Quebec
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Country [13]
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Finland
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State/province [13]
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Helsinki
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Country [14]
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France
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State/province [14]
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Marseille
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Country [15]
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France
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State/province [15]
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Paris
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Country [16]
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France
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State/province [16]
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Pessac Cedex
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Country [17]
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France
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State/province [17]
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Pierre Benite Cedex
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Country [18]
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France
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State/province [18]
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Toulouse cedex 9
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Country [19]
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Germany
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State/province [19]
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Niedersachsen
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Country [20]
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Israel
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State/province [20]
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Haifa
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Country [21]
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Korea, Republic of
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Seoul-teukbyeolsi [Seoul]
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Country [22]
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Korea, Republic of
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Seoul
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Singapore
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Singapore
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Country [24]
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Spain
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State/province [24]
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Barcelona
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Spain
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Madrid
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Country [26]
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Spain
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Valencia
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Country [27]
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Taiwan
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State/province [27]
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Taichung City
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Country [28]
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Taiwan
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State/province [28]
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Taipei
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Eli Lilly and Company
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Address
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Country
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Other collaborator category [1]
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Commercial sector/Industry
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Name [1]
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Loxo Oncology, Inc.
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Address [1]
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Ethics approval
Ethics application status
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Summary
Brief summary
This is an open-label, multi-center Phase 1 study of LY3410738, an oral, covalent isocitrate
dehydrogenase (IDH) inhibitor, in patients with IDH1 and/or IDH2-mutant advanced hematologic
malignancies who may have received standard therapy
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04603001
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Yin Zhang, MD
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Address
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Loxo Oncology
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Phone
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Fax
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Email
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Contact person for public queries
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Fax
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04603001
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