Relapsed or Refractory AML and other Hematologic Malignancies
Conditions
Interventions
KK2845 at each dose level administered by continuous intravenous infusion.
Sponsors
Noshiro Masayoshi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (Patients with Relapsed or Refractory Acute Myeloid Leukemia) 1. 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. 2. 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. 3. 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. (Patients with other Hematologic Malignancies) 1. Patients diagnosed with each type of Hematologic Malignancies. (Other criteria common to all eligible patients) 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 an ECOG PS of 0 to 2 on screening test. 4. 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 However, even if the neutrophil count is less than 500/mm3, if the principal investigator or sub investigator judges that the neutrophil count is expected to improve, enrollment in this study is acceptable. -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 However, even if the creatinine clearance calculated using the above formula is less than 50 mL/min, if the value is equal to or greater than 30 mL/min and the serum creatinine level is within 1.5 times the upper limit of the standard value, enrollment in this study is acceptable. -Cardiac function -LVEF of 50% or more (MUGA or ECHO) -QTcF < 450 msec for males and < 480 msec for females 5. Patients expected to survive longer than 3 months.
Exclusion criteria
Exclusion criteria: 1. Patients diagnosed with APL. 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 underwent a previous allogeneic hematopoietic stem cell transplant. However, enrollment in this trial is permitted if all of the following criteria are met: -At least 6 months have elapsed since allogeneic hematopoietic stem cell transplantation as of Cycle 1 Day 1. -The patient does not have active acute GvHD of Grade 2 or higher, nor active chronic GvHD of any severity. Acute GvHD is classified according to the MAGIC criteria (Harris et al., 2016), and chronic GvHD is classified according to the NIH criteria (Jagasia et al., 2015), by Grade or severity. Acute GvHD should be graded according to the MAGIC criteria (Harris et al., 2016), and chronic GvHD according to the NIH criteria (Jagasia et al., 2015). - At least 4 weeks have elapsed since the donor lymphocyte infusion at Cycle 1 Day 1. 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 inters
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity (Part 1:Dose escalation) | — |
Secondary
| Measure | Time frame |
|---|---|
| - 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 | — |
Contacts
Public ContactClinical trial information contact
Kyowa Kirin Co., Ltd.
Outcome results
None listed