Relapsed or Refractory AML and Other Hematologic MalignanciesPhase 1NCT06812104
Phase I Clinical Trial of KK2845 in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Other Hematologic Malignancies.
A Phase 1 study testing KK2845_1, KK2845_2 and KK2845_3 in people with Relapsed or Refractory AML and Other Hematologic Malignancies, run by Kyowa Kirin Co., Ltd. at 17 sites in Japan.
Trial summary
This is the first in human study of KK2845. This clinical trial consists of Part 1 (Dose Escalation) and Part 2 (Backfill). For patients with relapsed or refractory acute myeloid leukemia (AML) and other Hematologic Malignancies, in Part 1, the tolerability of KK2845 will be evaluated to determine the maximum… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory AML and Other Hematologic Malignancies
- What is being tested?
- KK2845_1, KK2845_2 and KK2845_3
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 156 participants
- Where
- 17 sitesJapan
- Study dates
- 10 Oct 2024to 30 Nov 2031
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 【Patients with Relapsed or Refractory Acute Myeloid Leukemia】
- 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.
- 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
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- 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 hypomethylating agent.
- 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】
- Patients who have given their free and voluntary written consent to participate in this clinical trial.
- Patients must be at least 18 years of age at the time consent is obtained.
- Patients with an ECOG PS of 0 to 2 on screening test.
- 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
- Patients who are expected to survive longer than 3 months.
Who cannot join
- Patients who are diagnosed with APL.
- Patients with suspected extramedullary disease.
- 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).
- 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.
- 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:
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- 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.
- 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
- Patients who received another investigational drug within 4 weeks or 5 times the half-life prior to Cycle 1 Day 1, whichever is shorter.
- Patients who underwent major surgery (excluding biopsy, central venous catheter insertion, and tooth extractions, etc.) within 4 weeks prior to Cycle 1 Day 1.
- Patients who received a live vaccine within 4 weeks prior to Cycle 1 Day 1.
- 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.
- Patients with the following infections.
- Required systemic treatment (including bacterial, viral, and fungal pathogens)
- Difficulty for 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.
- Patients who are 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).
- Patients with active interstitial lung disease (including drug-induced pneumonia) or a history of such disease.
- 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) is acceptable for enrollment in this study.
- 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.
- Patients with a history of arterial thrombosis (e.g., stroke, pulmonary embolism) within 6 months prior to the screening test.
- Patients with positive for HBV antigen or antibody, HCV antibody, HIV antibody, or HTLV-1 antibody at 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.
- Patients with acquired, unclassifiable or hereditary, primary, or secondary immunodeficiency.
- Patients with a history of Grade 3 or higher allergic reactions to antibody drugs, payloads, or excipients to KK2845.
- Patients who are pregnant, lactating (excluded from this study even if lactation is interrupted), potentially pregnant, or wishing to become pregnant during this study period.
- Patients with psychiatric disorders, central nervous system illnesses (e.g., encephalopathy), or social conditions that are judged to make compliance with the clinical trial difficult or affect obtaining written consent.
- Other patients who are considered to be undesirable to participate in this study by investigator or subinvestigator.
Trial locations and contacts
17 sites in 1 country. Contact the study team or a site near you to ask about taking part.
17 sites in 1 country
Japan17 sites, 17 recruiting
- Recruiting
Kyushu University Hospital
Fukuoka, 812-8582
- Recruiting
Fukushima Medical University Hospital
Fukushima, 960-1295
- Recruiting
Kansai Medical University Hospital
Hirakata, Osaka, 573-1191
- Recruiting
Kameda General Hospital
Kamogawa, Chiba, 296-8602
- Recruiting
Kanazawa University Hospital
Kanazawa, 920-8641
- Recruiting
Kurume University Hospital
Kurume, Fukuoka, 830-0011
- Recruiting
Dokkyo Medical University Hospital
Mibu, Tochigi, 321-0207
- Recruiting
Japanese Red Cross Musashino Hospital
Musashino, Tokyo, 180-8610
- Recruiting
Japanese Red Cross Nagasaki Genbaku Hospital
Nagasaki, 852-8104
- Recruiting
Okayama University Hospital
Okayama, 700-8558
- Recruiting
Kindai University Hospital
Osaka, 589-8511
- Recruiting
Saitama Medical University Hospital
Saitama, 350-0495
- Recruiting
Hokkaido University Hospital
Sapporo, Hokkaido, 060-8648
- Recruiting
Toranomon Hospital
Tokyo, 105-8470
- Recruiting
Juntendo University Hospital
Tokyo, 113-8431
- Recruiting
Nippon Medical School Hospital
Tokyo, 113-8603
- Recruiting
University of Fukui Hospital
Yoshida, Fukui, 910-1193
About this study
Official title: A Phase I, Multicenter, Non-controlled, Open-label, Non-randomized, Dose-escalation Study of KK2845 in Patients With Relapsed or Refractory Acute Myeloid Leukemia and Other Hematologic Malignancies.
This is the first in human study of KK2845. This clinical trial consists of Part 1 (Dose Escalation) and Part 2 (Backfill).
For patients with relapsed or refractory acute myeloid leukemia (AML) and other Hematologic Malignancies, in Part 1, the tolerability of KK2845 will be evaluated to determine the maximum tolerated dose (MTD). In Part 2, additional data will be collected by administering KK2845 at dose levels for which tolerability has been confirmed.
- Being tested
- KK2845_1, KK2845_2, KK2845_3, KK2845_4, KK2845_5
- Medical subject headings
- Recurrence, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KK2845_1Drug
KK2845 will be administered at several dose levels to determine maximum tolerated dose (MTD).
KK2845_2Drug
KK2845 will be administered at several dose levels to determine maximum tolerated dose (MTD).
KK2845_3Drug
KK2845 will be administered at several dose levels to determine maximum tolerated dose (MTD).
KK2845_4Drug
KK2845 will be administered at several dose levels to determine maximum tolerated dose (MTD).
KK2845_5Drug
KK2845 will be administered at several dose levels to determine maximum tolerated dose (MTD).
KK2845_6Drug
KK2845 will be administered at several dose levels to determine maximum tolerated dose (MTD).
KK2845_7Drug
KK2845 will be administered at several dose levels to determine maximum tolerated dose (MTD).
KK2845_8Drug
KK2845 will be administered at several dose levels to determine maximum tolerated dose (MTD).
KK2845_alternative_1Drug
KK2845 will be administered at several dose levels to collect additional data.
KK2845_alternative_2Drug
KK2845 will be administered at several dose levels to collect additional data.
| Study group | Role | What they receive |
|---|---|---|
| KK2845 to R/R AML_1 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_1 |
| KK2845 to R/R AML_2 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_2 |
| KK2845 to R/R AML_3 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_3 |
| KK2845 to R/R AML_4 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_4 |
| KK2845 to R/R AML_5 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_5 |
| KK2845 to R/R AML_6 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_6 |
| KK2845 to R/R AML_7 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_7 |
| KK2845 to R/R AML_8 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_8 |
| KK2845 to R/R AML_alternative_1 | Experimental | KK2845 will be administered at several dose levels to collect additional data. Receives: Drug: KK2845_alternative_1 |
| KK2845 to R/R AML_alternative_2 | Experimental | KK2845 will be administered at several dose levels to collect additional data. Receives: Drug: KK2845_alternative_2 |
| KK2845 to other Hematologic Malignancies_1 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_1 |
| KK2845 to other Hematologic Malignancies_2 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_2 |
| KK2845 to other Hematologic Malignancies_3 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_3 |
| KK2845 to other Hematologic Malignancies_4 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_4 |
| KK2845 to other Hematologic Malignancies_5 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_5 |
| KK2845 to other Hematologic Malignancies_6 | Experimental | KK2845 will be administered at several dose levels to determine MTD. Receives: Drug: KK2845_6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (Part 1：Dose escalation)
Measured: At the end of Cycle 1 (each cycle is 21 or 28 days)
Secondary outcomes (8)
Number of Adverse Events
Measured: Through study completion, an average of 1 year
Blood Drug Concentration
Measured: Pre-dose and post-dose at multiple timepoints for each cycle during the intervention (each cycle is 21 or 28 days)
Number of ADA (anti-KK2845 antibody) positive Participants
Measured: Through study completion, an average of 1 year
Best overall response (CR, CRh, CRi, MLFS, PR, Not evaluable, Relapsed disease, ORR)
Measured: Pre-dose for Cycle 1 Day1, Each end of the cycles (each cycle is 21 or 28 days), Inspection at Discontinuation
Duration of remission
Measured: Through study completion, an average of 1 year
Event-free survival
Measured: Through study completion, an average of 1 year
Time to remission
Measured: Through study completion, an average of 1 year
Overall Survival
Measured: During the treatment and every 12 weeks after study treatment completion (approximately up to 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2025
- Study start10 Oct 2024
- Primary completion30 Nov 2031 (estimated)
- Study completion30 Nov 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory AML and Other Hematologic MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 156 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kyowa Kirin Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kyowa Kirin Co., Ltd., Study director, Kyowa Kirin Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06812104
- Sponsor's protocol ID
- 2845-001
- Status last verified
- Jun 2026
- First submitted
- 23 Dec 2024
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is not a plan to make IPD available.