Phase I Clinical Trial of KK2845 in Patients with Relapsed or Refractory Acute Myeloid Leukemia

JRCT ID: jRCT2011240008

Registered date:21/04/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: relapsed or refractory acute myeloid leukemia
• Date of first enrollment: 27/05/2024
• Target sample size: 48
• Study type: Interventional
• Intervention(s): KK2845 at each dose level administered by continuous intravenous infusion.

Outcome(s)

• Primary Outcome: Dose-limiting toxicity (Part 1:Dose escalation)

Secondary Outcome

- Adverse event
- Clinical Laboratory Values
- Vital signs
- ECG
- Blood concentration
- ADA (anti-KK2845 antibody)
- Best overall response (CR, CRh, CRi, CR+CRh, PR, ORR, MLFS)
- Duration of remission
- EFS
- Time to response
- OS

Key inclusion & exclusion criteria

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

Include criteria

1. Patients who have given their free and voluntary written consent to participate in this clinical trial.
2. Patients must be at least 18 years of age at the time consent is obtained.
3. Patients with a confirmed diagnosis of AML according to the WHO classification (2022 edition)by pathological examination at the performing institution conducted as screening test.
4. Patients who meet the following definition of relapsed or refractory.
Relapse: Patients with any of the following relapse findings after achieving CR, CRh, or CRi.
-Myeloblasts >5%
-Blood blasts reappear in two peripheral blood samples at least one week apart
Refractory: Patients who have failed to achieve CR, CRh, or CRi after a sufficient duration of initial intense chemotherapy or initial treatment with venetoclax or demethylation inhibitor.
5. Patients who are considered to have no standard treatment with sustained remission, who have failed to complete a potentially curative treatment, who have no treatment with a promising therapeutic effect, or who have refused standard treatment.
6. Patients with an ECOG PS of 0 to 2 on screening test.
7. Patients with hematopoietic, hepatic, renal, and cardiac function that meet all of the following criteria on screening test.
-Hematopoietic capacity
-Neutrophil count greater than 500/mm3
-Liver function
-AST within 3.0 times the upper reference limit
-ALT within 3.0 times the upper reference limit
-T-Bil within 1.5 times the upper limit of the standard
-Kidney function
-Creatinine clearance (Cockcroft-gault formula) equal to or greater than 50 mL/min
-Cardiac function
-LVEF of 50% or more (MUGA or ECHO)
-QTcF < 450 msec for males and < 480 msec for females
8. Patients expected to survive longer than 3 months.

Exclude criteria

1. Patients diagnosed with APML.
2. Patients with suspected extramedullary disease.
3. Patients with a history of malignancy other than those listed in the inclusion criteria or with active malignancy other than those listed in the inclusion criteria (resected localized basal cell carcinoma and localized squamous cell carcinoma of the skin, resected noninvasive cervical cancer, resected noninvasive breast cancer, and cancers for which the last curative treatment was given more than 5 years ago are eligible for enrollment).
4. Patients with white blood cell count greater than 25000/mm3 (If treatment with hydroxyurea results in a white blood cell count of 25000/mm3 or less, enrollment in this study is acceptable) on screening test.
5. Patients who have received a previous hematopoietic stem cell transplant.
6. Patients who have received anti-tumor therapy such as anticancer agents or radiotherapy (except for patients taking hormone therapy as adjuvant maintenance therapy for breast or prostate cancer prior to the start of study treatment) within the following time periods prior to Cycle 1 Day 1.
-anticancer agents: 2 weeks (If hydroxyurea is used to control blasts, registration is acceptable for use up to Day -1)
-Hormone therapy: 2 weeks
-Radiation therapy: 4 weeks
-Unapproved medical devices: 4 weeks
7. Patients who received another investigational drug within 4 weeks prior to Cycle 1 Day 1 or 5 times the half-life, whichever is shorter.
8. Patients undergoing surgery (excluding biopsy and central venous catheter insertion) within 4 weeks prior to Cycle 1 Day 1.
9. Patients who received a live vaccine within 4 weeks prior to Cycle 1 Day 1.
10. Patients who have not recovered to Grade 1 or below from an adverse event caused by previously administered anti-tumor therapy.
However, patients with alopecia or laboratory abnormalities within the range described in the selection criteria or patients experiencing Grade 2 chronic adverse events may be enrolled in this study if the investigator or subinvestigator determines that the safety evaluation of the subject will not be affected.
11. Patients with the following infections.
-Require systemic treatment (including bacterial, viral, and fungal pathogens)
-Difficulty in initiating anti-tumor therapy
However, patients with infections controlled by antibiotic or antiviral therapy, or patients receiving prophylactic antibiotic or antiviral therapy, may be enrolled in this study.
12. Patients with suspected SARS-CoV-2 infection (e.g., patients with mild infectious findings and a positive SARS-CoV-2 test without subsequent documentation of a negative test result, patients suspected of ongoing infection based on clinical characteristics).
13. Patients with active interstitial lung disease (including drug-induced pneumonia) or a history of such disease.
14. Patients who have received continuous systemic administration (oral or intravenous) of steroids or other immunosuppressive drugs within 4 weeks prior to Cycle 1 Day 1.
However, topical, inhalation use, and low-dose corticosteroids (equivalent to 10 mg/day of prednisolone) may be enrolled in this study.
15. Patients with a history of clinically severe cardiovascular disease (e.g., complete left bundle branch block, uncontrolled ventricular fibrillation, uncontrolled ventricular arrhythmia, angina pectoris, myocardial infarction, prolonged QT syndrome, NYHA grade III or IV congestive heart failure) within 6 months prior to screening test.
16. Patients with a history of arterial thrombosis (stroke, pulmonary embolism, etc.) within 6 months prior to the screening test.
17. Patients with a positive for HBV antigen or antibody, HCV antibody, HIV antibody, or HTLV-1 antibody on screening test. However, the following cases are acceptable for enrollment in this clinical trial.
-HBV test at screening test is negative for HBs antigen and positive for either HBc or HBs antibody or both, but HBV-DNA test is below the lower limit of quantification or below 20 IU/mL (1.3 LogIU/mL)
-Clear history of hepatitis B vaccination and positive HBs antibody alone
-Negative HCV nucleic acid amplification test (HCV-RNA test) with positive HCV antibody test at screening test
18. Patients with acquired, unclassifiable or hereditary, primary or secondary immunodeficiency.
19. Patients with a history of Grade 3 or higher allergic reactions to antibody drugs, payloads, or additives to investigational drugs.
20. Pregnant women, lactating women (who are excluded from the study even if lactation is interrupted), those who may be pregnant, or patients who wish to become pregnant during the study period.
21. Patients with psychiatric disorders, central illnesses (e.g., encephalopathy), or social conditions that are judged to make compliance with the clinical trial difficult or affect obtaining written consent.
22. Other patients whom the investigator or subinvestigator determines to be inadvisable to participate in this study.

Related Information

• Primary Sponsor: Noshiro Masayoshi