A Phase I Study of NS-917 in Japanese Patients With Relapsed or Refractory Acute Myeloid Leukemia

JRCT ID: jRCT2031210452

Registered date:26/11/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Acute Myeloid Leukemia
• Date of first enrollment: 17/02/2022
• Target sample size: 6
• Study type: Interventional
• Intervention(s): NS-917 at a dose of at 6mg/m2/day administered by continuous infusion for 14 consecutive days followed by 14-day resting period per 28-day cycles.

Outcome(s)

• Primary Outcome: To determine the dose-limiting toxicity (DLT) and perform pharmacokinetic (PK) studies of NS-917 in patients with relapsed or refractory acute myeloid leukemia.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Ages 20 years and over.
2. Subjects diagnosed with AML in the WHO (World Health Organization) classification (2017 ver.).
3. Subjects diagnosed with AML that has relapsed after, or is refractory to, two or three prior induction regimens that may have included intensive chemotherapy (e.g.,venetoclax). In addition, if subjects with a history of IPSS-R high or very high risk myelodysplastic syndrome and treated with hypomethylating drugs, such treatment may be counted as one regimen, but subjects have to be treated another regimen*after diagnosed with AML.
* If subjects relapsed after remission and was treated with the same induction therapy as the initial induction for AML, it can be counted as another regimen.
4. ECOG Performance Status of 0, 1 or 2.
5. Adequate clinical laboratory values (i.e., plasma creatinine < 1.5 x upper limit of normal (ULN) for the institution, bilirubin < 1.5 x ULN, alanine transaminase (ALT) and aspartate transaminase (AST) < 2.5 x ULN) within 3 days prior to treatment.
6. Male and female Subjects must agree to use acceptable contraceptive methods for the duration of the study and for at least six months after the discontinuation of study treatment. No consent required for female Subjects who are not likely to become pregnant after menopause (more than one year after the last menstruation without any other medical reason) or due to uterine /ovariectomy, etc.
7. Signed informed consent prior to the start of any study-specific procedures.
8. Subjects who are expected to survive for 12 or longer weeks after the start of treatment.

Exclude criteria

1. Subjects have acute promyelocytic leukemia (APL).
2. Subjects with active CNS involvement by leukemia.
3. Current malignancies of another type. Exceptions: Subjects could participate if they had previously treated and currently controlled prostate cancer, adequately treated in situ cervical cancer, basal cell skin cancer, or other malignancies with no evidence of disease for 2 years or more. The disease-free period is the period during which remission is maintained without anticancer treatment, and surgery or hormone therapy after remission is not included in anticancer treatment.
4. The interval from prior treatment to time of study drug administration was < 2 weeks for cytotoxic agents or < 5 half-lives for noncytotoxic agents. If the side effects of prior treatment continue, the Subjects should be relieved to grade 1 or lower based on CTCAE v5.0 before starting study drug administration. Hydroxyurea for disease control can be used until the start of study drug administration.
5. Extensive prior radiotherapy for AML.
6. Prior bone marrow/stem cell transplantation.
7. Subjects with serious and uncontrolled complications.
8. Subjects with mental illness who has difficulty obtaining consent.
9. Subjects with the New York Heart Association (NYHA) functional class III or IV.
10. Uncontrolled intercurrent illnesses, including active or uncontrolled infections.
If subjects are receiving intravenous antibiotics prior to the start of study drug administration, inclusion judgement will be determined after discussion with the sponsor.
11. Subjects with clinically significant bleeding disorders.
12. Subjects with HIV antibody positive, HBV antigen positive or anti-HCV antibody positive.
13. Subjects have previously treated and currently controlled interstitial pneumonia.
14. Subjects have experience in hypersensitivity reactions with pharmaceutical ingredients in NS-917.
15. Subjects receiving any other study drugs or unapproved drugs within 28 days prior to treatment.
16. A pregnant or lactating woman. For female Subjects, a pregnancy test is performed during the observation period. However, it is not necessary for Subjects who are not likely to become pregnant after menopause (one year or more after the last menstruation without other medical reasons) or due to uterine/ovariectomy, etc. Lactating woman cannot be included in the study due to interruption of lactation.
17. Subjects deemed unsuitable by the principal investigator or sub-investigator.
18. Subjects with a neutrophil count of less than 500/uL at the time of informed consent and within 3 days (planned) prior to the start of administration of the study drug, and judged to be unsuitable after discussion with the sponsor.

Related Information

• Primary Sponsor: Higashioka Masaya