Phase I study of OP-2100 in patients with relapsed or refractory high-risk myelodysplastic syndrome or high-risk chronic myelomonocytic leukemia

JRCT ID: jRCT2071220035

Registered date:04/08/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Patients with MDS or CMML who are relapsed or refractory or intolerant to standard of care.
• Date of first enrollment: 31/08/2022
• Target sample size: 9
• Study type: Interventional

Intervention(s)

Administration method:Orally administer the investigational drug once daily for 5 consecutive days followed by a treatment interruption for 23 days as one treatment cycle of 28 days. Continue administering the investigational drug with the same treatment regimen for the second and subsequent treatment cycles unless the patient experiences an exacerbation of the primary disease, unacceptable toxicity, or meets other discontinuation criteria.

Dose:The investigational drug will be administered at the dose levels shown in the table below. In Cycle 1, the investigational drug will be administered according to the dose levels specified by the sponsor. It will not be acceptable to change the dose of the investigational drug after the start of protocol treatment unless the patient meets the dose reduction criteria for the investigational drug. After Level 4, the dose will be determined based on the tolerability, safety, and PK with an incremental amplification of 33% or less.

Level 3: 120 mg
Level 2: 80 mg
Level 1 (initial dose): 50 mg
Level -1: 30 mg

Outcome(s)

• Primary Outcome: Primary endpoint: Incidence rate of DLT(Dose limiting toxicity)in Cycle 1

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Japanese patients who meet all of the following criteria will be selected.
(1) Patients who are able to provide written informed consent using the informed consent form.
(2) Patients with MDS or CMML who are relapsed or refractory, or intolerant to standard therapy with a treatment history with standard therapy, including therapies known to provide clinical benefit, at the time of informed consent, and who meet any of the following criteria. Regardless of the presence or absence of a treatment history, if standard therapy is contraindicated.
Patients who are diagnosed with MDS according to the WHO classification (2016)and meet the criteria for the very high, high or intermediate risk group specified by IPSS-R.
Diagnosed with CMML-1 or CMML-2 according to the WHO classification (2016).
(3) Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of >=2.
(4) Patients with a life expectancy of >=12 weeks at the time of informed consent assessed by the investigator or subinvestigator.
(5) Patients aged >=18 years at the time of informed consent.
(6) Patients who meet the following criteria within 14 days before the start of the study treatment (ULN is the upper limit of the institutional reference range):
Serum creatinie level<=2 xULN
Total bilirubin level<=2 xULN
AST,ALT<=2.5 xULN
SpO2>=90% (room air)
All other non-hem%tologic toxicity scores affected by prior treatment have resolved to<=Grade1.
(7)Patients or their partners who have menstruation must agree to use contraception *before the study initiation (after informed consent), during the study period and for 180 days after the last dose of investigational drug.
*Use of condom, intrauterine device (IUD), contraceptive diaphragm (not certified in Japan), spermicide (not approved in Japan), or oral contraceptives for at least 4 weeks before the start of study treatment. However, the possibility that the study treatment induces drug-metabolizing enzymes such as CYP3A cannot be ruled out; therefore, if oral contraceptives are to be used, patients are required to concomitantly use appropriate contraceptive methods such as condom, IUD, contraceptive diaphragm (not certified in Japan), and spermicide (not approved in Japan).

Exclude criteria

Patients will be excluded from the study if they meet any of the following criteria:
(1) Patients with dry tap bone marrow.
(2) Patients who have received or are scheduled to receive hematopoietic stem cell transplantation.
(3) Patients who have received chemotherapy, immunosuppressive therapy, radiotherapy, other investigational drug, or privately imported drugs within 28 days before the start of study treatment.
(4) Patients who received G-CSF preparations, M-CSF preparations, GM CSF preparations, erythropoietin preparations, or thrombopoietin receptor-agonists within 14 days before the start of study treatment.
(5) Patients who are pregnant (including those judged to be possibly pregnant based on medical interview, etc.) or lactating (not allowed to be enrolled even after discontinuation of breastfeeding).
(6) Patients with suspected hypersensitivity to any of the components (including excipients) of the investigational drug.
(7) Patients with double cancer (disease-free period <-3 years) (excluding lesions equivalent to intraepithelial cancer or intramucosal cancer considered to have been cured by local treatment).
(8) Patients tested positive for HIV antibody, HBs antigen, HBs antibody, HBc antibody, or HCV antibody. However, patients may be enrolled if tested negative for HBs antigen and HBV-DNA, even if they tested positive for HBs antibody or HBc antibody. Patients may be enrolled if they tested negative for HCV-RNA, even if they tested positive for HCV antibody.
(9) Patients with active uncontrolled infection.
(10) Patients with significant active cardiac disease.
(11) Patients with clinically significant gastrointestinal abnormalities that may interfere with swallowing of investigational drug or alter the absorption of investigational drug
(12) Patients who were assessed as ineligible for the study by the investigator or subinvestigator for any other reason.

Related Information

• Primary Sponsor: Yuuki Nukazuka