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)
- Conditions
- Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)Relapsed/Refractory (R/R) Higher Risk Myelodysplastic Syndrome (MDS)
- Registration Number
- JPRN-jRCT1080224851
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 43
1. Subjects is considered an adult according to local regulation at the time of signing the informed consent form.
2. Subject diagnosed with R/R AML or R/R higher risk MDS is defined as:
a. R/R AML 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 all standard therapies including targeted therapies (unless the therapy is contraindicated or intolerable) which are known to provide clinical benefit; and received salvage therapy or is not a candidate for salvage therapy.
b. R/R higher risk MDS: Has MDS by the WHO criteria (2016); and either relapsed after achieving remission or refractory to standard therapies, including >= 4 cycles of hypomethylating agents (unless the therapy is contraindicated or intolerable); and is classified as higher risk MDS with a score of > 3.5 by Revised International Prognostic Scoring System (IPSS-R) in MDS.
3. Subject has an Eastern Cooperative Oncology Group performance status of <= 2.
4. Subject must meet the following criteria as indicated on the clinical laboratory tests during screening period:
a. Serum aspartate aminotransferase and alanine aminotransferase <= 2.5 x upper limit of normal (ULN).
b. Serum total bilirubin <= 1.5 x ULN.
c. Serum creatinine <= 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
d. Platelets >= 50,000/microL at cycle 1 day 1 (C1D1) in the dose escalation cohorts only.
5. Subject has a life expectancy of >= 12 weeks at the time of screening.
6. Subjects with AML must have peripheral blood absolute blast count of < 20,000/microL at C1D1.
7. Female subject is not pregnant and at least 1 of the following conditions apply:
a. Not a woman of childbearing potential (WOCBP).
b. WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 180 days after final study treatment administration.
8. 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.
9. 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.
10. 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.
11. Male subject must not donate sperm during the treatment period and for 180 days after the final study treatment administration.
12. 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.
13. Subject agrees not to participate in another interventional study while receiving study treatment in the present study.
1. Subject was diagnosed with acute promyelocytic leukemia.
2. Subject has breakpoint cluster region-Abelson-positive leukemia (BCR-ABL).
3. 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).
4. Subject has received any of the following therapies:
a. Systemic immunomodulators or immunosuppressive drugs including steroids <= 28 days prior to C1D1 (steroids can be used if not intended for treatment of AML or MDS; steroids for AML/MDS related symptoms can be used at low doses [less than 10 mg/day dexamethasone]).
b. Cytotoxic agents (except hydroxyurea given for controlling blast cells) <= 28 days prior to C1D1.
c. Investigational products for the treatment of AML or MDS within 5 half-lives prior to screening visit.
d. Hematopoietic stem cell transplant (HSCT).
e. Radiation therapy <= 28 days prior to C1D1.
5. Subject has clinically active nervous system leukemia.
6. Subject has active or prior documented autoimmune or inflammatory disorders requiring systemic treatment.
7. Subject has ongoing, untreated malignancy with the exception of the following:
a. 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.
b. 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.
8. Subject with left ventricular ejection fraction of < 45% on echocardiogram or multigated acquisition scan (MUGA) performed within 28 days of screening.
9. Subject has laboratory abnormalities, or clinical evidence of disseminated intravascular coagulation, or ongoing history of coagulation disorder manifested by bleeding or clotting.
10. Subject has an active uncontrolled infection.
11. Subject is known to have human immunodeficiency virus infection.
12. Subject has active hepatitis B or C or other active hepatic disorder.
13. Subject has any condition which makes the subject unsuitable for study participation.
14. Subject has a known or suspected hypersensitivity to bovine-derived protein or has suspected hypersensitivity to any ingredients of ASP7517.
15. Subject is eligible for HSCT.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1.Incidence of dose limiting toxicities (DLTs)<br>2.Adverse Events (AEs) / Serious Adverse Events (SAEs) / Laboratory values / Vital signs / Routine 12-lead electrocardiogram (ECG)/Physical exam<br>3.Eastern Cooperative Oncology Group (ECOG) performance status<br>4.Composite complete remission (CRc) rate for participants with R/R AML (phase 2)<br>5.Complete remission + bone marrow complete remission + partial remission (CR + BM CR + PR) rate for participants with R/R higher risk MDS (phase 2)
- Secondary Outcome Measures
Name Time Method 1.Duration of remission <br>2.Number of participants with event-free survival (EFS)<br>3.Duration of overall survival (OS) <br>4.CR rates for participants with R/R AML<br>5.Best response (CRc + PR) rates for participants with R/R AML<br>6.Complete remission with partial hematologic recovery (CRh) rates for participants with R/R AML<br>7.CR rates for participants with R/R higher risk MDS<br>8.Hematologic improvement (HI) rates for participants with R/R higher risk MDS<br>9.Objective response (CR + BM CR + PR + HI) rates for participants with R/R higher risk MDS