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A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)

NCT04079296

Description:

The purpose of this study is to evaluate the safety and tolerability and to determine the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) of ASP7517. This study will also evaluate the clinical response of ASP7517 as well as other measures of anticancer activity of ASP7517.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)
  • Official Title: A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP7517 in Subjects With Relapsed/Refractory Acute Myeloid Leukemia (AML) and Relapsed/Refractory Higher Risk Myelodysplastic Syndrome (MDS)

Clinical Trial IDs

  • ORG STUDY ID: 7517-CL-0101
  • NCT ID: NCT04079296

Conditions

  • Acute Myeloid Leukemia (AML)
  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
ASP7517Phase 2 ASP7517 Dose Expansion

Purpose

The purpose of this study is to evaluate the safety and tolerability and to determine the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) of ASP7517. This study will also evaluate the clinical response of ASP7517 as well as other measures of anticancer activity of ASP7517.

Detailed Description

      This study consists of 2 parts: phase 1 dose escalation and phase 2 dose expansion.

      Phase 1 Dose Escalation:

      Approximately 18 subjects with either relapsed/refractory (R/R) AML or R/R higher risk MDS
      will be enrolled. Participants will receive 2 single doses of ASP7517 via intravenous
      infusion. Dosing will occur on day 1 of each cycle. Each cycle is defined as 28 days with a
      total of 2 treatment cycles.

      Participants must be managed under hospitalization for at least 7 days during the first cycle
      of the dose escalation phase. In addition, prior to hospital discharge, participant safety
      must be ensured by performing medical tests and procedures listed on day 8 of cycle 1 and
      tests considered clinically necessary to evaluate the participant's general condition and
      adverse event (AE) resolution. The participant should also be followed on an outpatient basis
      on planned visits during cycles 1 and 2 after hospital discharge during the dose limiting
      toxicity (DLT) assessment period to closely monitor any AEs.

      Phase 2 Dose Expansion:

      Approximately 104 participants per dose level will be enrolled. Each dose level may enroll up
      to 52 R/R AML participants and up to 52 R/R higher risk MDS participants. Both groups of
      participants will enroll in parallel and independently. The number of dose levels
      investigated during phase 2 will be based upon the data from phase 1. When escalation and
      expansion cohorts are both open for enrollment, enrollment into escalation cohorts takes
      priority such that participants who are eligible for both will be preferentially enrolled in
      the escalation cohorts.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1 ASP7517 Dose EscalationExperimentalTwo single doses of ASP7517 will be administered intravenously at up to 3 dose levels and will be based on the assessment of safety variables, including the occurrence of dose limiting toxicities (DLTs).
  • ASP7517
Phase 2 ASP7517 Dose ExpansionExperimentalTwo single doses of ASP7517 will be administered intravenously at the dose levels determined from the Dose Escalation phase.
  • ASP7517

Eligibility Criteria

        Inclusion Criteria:

          -  Subject diagnosed with R/R AML or R/R higher risk MDS is defined as:

               -  R/R AML: Morphologically documented primary or secondary AML by the WHO criteria
                  (2016); and refractory to at least 2 cycles of induction chemotherapy/not a
                  candidate for re-induction or relapsed after achieving remission with a prior
                  therapy; and received salvage therapy or is not a candidate for salvage therapy.

               -  R/R higher risk MDS: Has MDS by the WHO criteria (2016); and either relapsed
                  after achieving remission or refractory to chemotherapy; and is classified as
                  higher risk MDS with a score of > 3.5 by Revised International Prognostic Scoring
                  System (IPSS-R) in MDS.

          -  Subject has an Eastern Cooperative Oncology Group performance status of ≤ 2.

          -  Subject must meet the following criteria as indicated on the clinical laboratory tests
             during screening period:

               -  Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × upper limit
                  of normal (ULN).

               -  Serum total bilirubin ≤ 1.5 × ULN.

               -  Serum creatinine ≤ 1.5 × ULN or an estimated glomerular filtration rate of > 50
                  mL/min as calculated by the Modification of Diet in Renal Disease equation.

          -  Platelets ≥ 50,000/μL at cycle 1 day 1 (C1D1) in the dose escalation cohorts only.

          -  Subject has a life expectancy of ≥ 12 weeks at the time of screening.

          -  Subjects with AML must have peripheral blood absolute blast count of < 20,000/μL at
             C1D1. Note: Blast count can be controlled by hydroxyurea during screening period.

          -  Female subject is not pregnant and at least 1 of the following conditions apply:

               -  Not a woman of childbearing potential (WOCBP).

               -  WOCBP who agrees to follow the contraceptive guidance from the time of informed
                  consent through at least 180 days after final study treatment administration.

          -  Female subject must agree not to breastfeed starting at screening and throughout the
             study period and for 180 days after the final study treatment administration.

          -  Female subject must not donate ova starting at first dose of investigational product
             (IP) and throughout the study period and for 180 days after final study treatment
             administration.

          -  Male subject with female partner(s) of childbearing potential (including breastfeeding
             partner) must agree to use contraception throughout the treatment period and for 180
             day after final study treatment administration.

          -  Male subject must not donate sperm during the treatment period and for 180 days after
             the final study treatment administration.

          -  Male subject with pregnant partner(s) must agree to remain abstinent or use a condom
             for the duration of the pregnancy throughout the study period and for 180 days after
             final study treatment administration.

          -  Subject agrees not to participate in another interventional study while receiving
             study treatment in the present study.

        Exclusion Criteria:

          -  Subject was diagnosed with acute promyelocytic leukemia.

          -  Subject has breakpoint cluster region-Abelson-positive leukemia (BCR-ABL).

          -  Subject has persistent non-hematological toxicities of ≥ grade 2 (National Cancer
             Institute's Common Terminology Criteria for Adverse Events [NCI-CTCAE], version 5.0),
             with symptoms and objective findings from prior AML or MDS treatment (including
             chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation or
             surgery).

          -  Subject has received any of the following therapies:

               -  Systemic immunomodulators or immunosuppressive drugs including steroids ≤ 28 days
                  prior to C1D1.

               -  Cytotoxic agents (except hydroxyurea given for controlling blast cells) ≤ 28 days
                  prior to C1D1.

               -  Investigational products for the treatment of AML or MDS within 5 half-lives
                  prior to screening visit.

               -  Hematopoietic stem cell transplant (HSCT).

               -  Radiation therapy ≤ 28 days prior to C1D1.

          -  Subject has clinically active nervous system leukemia.

          -  Subject has active or prior documented autoimmune or inflammatory disorders requiring
             systemic treatment.

          -  Subject has ongoing, untreated malignancy with the exception of the following:

               -  Subjects with treated non-melanoma skin cancer, in situ carcinoma or cervical
                  intraepithelial neoplasia, regardless of the disease-free duration, are eligible
                  for this study if definitive treatment for the condition has been completed.

               -  Subjects with organ-confined prostate cancer with no evidence of recurrent or
                  progressive disease are eligible if hormonal therapy has been initiated or the
                  malignancy has been surgically removed or treated with definitive radiotherapy.

          -  Subject with left ventricular ejection fraction of < 45% on echocardiogram or
             multigated acquisition scan (MUGA) performed within 28 days of screening.

          -  Subject has laboratory abnormalities, or clinical evidence of disseminated
             intravascular coagulation, or ongoing history of coagulation disorder manifested by
             bleeding or clotting.

          -  Subject has an active uncontrolled infection.

          -  Subject is known to have human immunodeficiency virus infection.

          -  Subject has active hepatitis B or C or other active hepatic disorder.

          -  Subject has any condition which makes the subject unsuitable for study participation.

          -  Subject has a known or suspected hypersensitivity to bovine-derived protein or has
             suspected hypersensitivity to any ingredients of ASP7517.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLTs)
Time Frame:28 days
Safety Issue:
Description:A DLT is defined as any of the following events that occur within 28 days starting with the first dose on cycle 1 day 1 (C1D1) and that is considered to be related to investigation product (IP). The severity of AEs will be assessed according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. DLT is defined as follows: non-hematologic AEs that are ≥ grade 3; confirmed Hy's law case; new onset of grade 4 thrombocytopenia (with minimum of 2 grade worsening from baseline) within 24 hours of dosing; prolonged myelosuppression, defined as absolute neutrophil count (ANC) < 500/μL for more than 28 days off therapy and in the absence of evidence of active leukemia or MDS in the marrow or blood, will be considered as a DLT.

Secondary Outcome Measures

Measure:Duration of remission for participants with AML
Time Frame:Up to 2 years
Safety Issue:
Description:Duration of remission for participants with AML includes duration of CRc, duration of CR/complete remission with partial hematologic recovery (CRh), duration of CRh, duration of CR, and duration of response (i.e., CRc + PR).
Measure:Duration of remission for participants with MDS
Time Frame:Up to 2 years
Safety Issue:
Description:Duration of remission for MDS includes duration of CR and duration of response (i.e., CR + PR).
Measure:Number of participants with event-free survival (EFS)
Time Frame:Up to 2 years
Safety Issue:
Description:EFS is defined as the time from the date of first dose until the date of documented relapse, treatment failure or death from any cause within 30 days after the last dose of study drug (whichever occurs first earliest of [relapse date, treatment failure date, death date] - first dose date + 1).
Measure:Duration of overall survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:OS is defined as the time from the date of first dose until the date of death from any cause (death date - first dose date + 1).
Measure:CR rates for participants with R/R AML
Time Frame:Up to 2 years
Safety Issue:
Description:CR rate is defined as the number of participants who achieve CR at any of the postbaseline visits divided by the number of participants in the analysis population.
Measure:Best response (CRc + PR) rates for participants with R/R AML
Time Frame:Up to 2 years
Safety Issue:
Description:Best response rate is defined as the number of subjects who achieve CRc or PR at any of the postbaseline visits divided by the number of subjects in the analysis population.
Measure:CRh rates for participants with R/R AML
Time Frame:Up to 2 years
Safety Issue:
Description:CRh rate is defined as the number of participants who achieve CRh at any of the postbaseline visits divided by the number of participants in the analysis population.
Measure:CR rates for participants with R/R higher risk MDS
Time Frame:Up to 2 years
Safety Issue:
Description:CR rate is defined as the number of participants who achieve CR at any of the postbaseline visits divided by the number of participants in the analysis population.
Measure:Hematologic improvement (HI) rates for participants with R/R higher risk MDS
Time Frame:Up to 2 years
Safety Issue:
Description:HI requires 1 measurement of erythroid or platelets or neutrophils maintained at a specified level for at least 8 weeks without ongoing cytotoxic therapy
Measure:Objective response (CR + PR + HI) rates (ORR) for participants with R/R higher risk MDS
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the number of participants who achieve CR or PR or HI at any of the postbaseline visits divided by the number of participants in the analysis population.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • ASP7517
  • Safety
  • Efficacy
  • Tolerability

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