Trial Title:
Study of YK012 in B-cell Acute Lymphoblastic Leukemia
NCT ID:
NCT06580301
Condition:
B-cell Acute Lymphoblastic Leukemia
Conditions: Official terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
YK012
Description:
The treatments include 2 cycles of induction treatment, 3 cycles of consolidation
treatment, and up to 5 cycles of maintenance treatment.
Arm group label:
YK012
Other name:
YK012 for Injection
Summary:
The purpose of this study is to assess the safety, tolerability, pharmacokinetics and
preliminary anti-tumor activity of YK012 administered as monotherapy in participants with
B-cell acute lymphoblastic leukemia (B-ALL).
Detailed description:
YK012 is a bispecific antibody designed to link B cells and T cells resulting in T-cell
activation and a cytotoxic T-cell response against cluster of differentiation (CD)19
expressing cells. Relapsed/refractory B-ALL in adult patients is an aggressive malignant
disease with dismal prognosis. This study is designed in 2 parts as described below:
Phase Ib (dose escalation) and Phase II (dose expansion). If in Phase Ib it is observed
in adult subjects at doses with manageable risk and antitumor activity, studies in
pediatric subjects can be initiated to explore safety and efficacy in pediatric subjects,
as well as pharmacokinetic profiles.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Participants or their legally acceptable representative must sign an ICF indicating
that the participants understand the purpose of, and procedures required for the
study and are willing to participate in the study.
2. Eastern Cooperative Oncology Group Performance Status (ECOG) of 0-2.
3. An estimated survival time of more than 12 weeks.
4. A definitive diagnosis of CD19-positive B-cell acute lymphoblastic leukemia with any
of the following conditions:
1. Ph-negative B-ALL with any of the following: i. Failure to achieve complete
remission after initial induction therapy. ii. Failure to achieve complete
remission after salvage treatment. iii. Relapse with first remission duration
≤12 months. iv. Second or later relapse. v. Relapse after hematopoietic stem
cell transplantation (HSCT).
2. Ph-positive B-ALL: failure to 1 or more tyrosine kinase inhibitors (TKIs), or
intolerance to treatment with TKIs, or with the T315I mutation.
5. ≥ 5% blasts in the bone marrow by morphologic assessment.
6. Recovery to Grade 0-1 (Graded by National Cancer Institute Common Toxicity Criteria
for Adverse Events (NCI CTCAE) Version (v) 5.0) from adverse events related to prior
therapy except alopecia.
7. Adequate hematological and organ function.
8. Female participants of childbearing potential must have a negative serum pregnancy
test at screening. Female patients who are sexually active must use highly effective
methods of contraception throughout the study and for 3 months following the last
dose of study treatment.
9. Male participants must agree to use reliable methods of contraception (barrier
methods or sexual abstinence) and avoid sperm donation throughout the study period
and until 3 months after the last dose.
Exclusion Criteria:
1. Burkitt´s Leukemia according to World Health Organization (WHO) classification.
2. History of antitumor therapy as follows, before the first dose of study drug:
1. Targeted therapy with small molecule drug within 2 weeks or 5 half-lives,
whichever is longer
2. Targeted therapy with macromolecular drug or Immunomodulatory agent therapy
within 3 weeks
3. Radiotherapy or chemotherapy (except for intrathecal chemotherapy and
dexamethasone), or treatment with Chinese traditional/patent medicine that has
definite antitumor effect within 2 weeks
4. Treatment with an investigational drug within 4 weeks or 5 half-lives,
whichever is shorter
5. Receipt of any live attenuated vaccines or live virus vaccine within 4 weeks
6. Autologous stem cell transplantation within 6 weeks
7. History of organ transplant, or allogeneic stem cell transplantation within 12
weeks.
3. Any active acute graft-versus-host disease (GvHD), grade 2-4 (according to
Glucksberg criteria) or active chronic GvHD requiring systemic treatment.
4. Other malignancy within 5 years, except localized malignancies that have been
adequately treated or free of the disease for ≥ 5 years, e.g., basal cell carcinoma
of the skin, squamous cell carcinoma of the skin, non-muscle invasive bladder
cancer, localized prostate cancer, carcinoma in situ of the cervix, carcinoma in
situ of the breast.
5. Active central nervous system (CNS) involvement or meningeal involvement with
clinical signs, or other evidence of uncontrolled metastases to the CNS or meninges,
judged by the investigator.
6. a. History of or current relevant CNS pathology as epilepsy, seizure, paresis,
aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain
syndrome, psychosis. b. Evidence for presence of inflammatory lesions and/or
vasculitis on cerebral MRI.
7. History or evidence of cardiovascular disease, including:
1. Acute coronary syndromes (e.g., myocardial infarction, unstable angina)
2. Coronary angioplasty or stenting within 6 months prior to enrollment
3. Clinically significant unstable arrhythmias (e.g., atrial fibrillation),
however, atrial fibrillation has been controlled for over 30 days prior to the
first dose of YK012 were allowed
4. New York Heart Association (NYHA) stage III or higher congestive heart failure
5. Left ventricular ejection fraction (LVEF) below lower limit of the study
center, or LVEF<50% if there is no lower limit at the study center
6. The Fridericia-corrected QT interval (QTcF, mean of triplicate measurements) ≥
470 msec (female) or ≥ 450 msec (male)
7. Implantable defibrillator
8. Clinically uncontrollable hypertension (i.e., SBP≥160 mm Hg and/or DBP≥100 mm
Hg).
8. Known allergy to monoclonal antibody drugs or exogenous immunoglobulin.
9. History of CD19 targeted therapy and positive test result for immunogenicity of
YK012 at screening.
10. Any major organ surgery or significant trauma within 4 weeks prior to the first dose
of YK012, or those requiring elective surgeries during the study, and all AEs
associated with surgery or significant trauma have not recovered to Grade ≤1 or
baseline graded by CTCAE v5.0 before the first dose of the YK012.
11. Regular dose of systemic corticosteroids during 4 weeks prior to initiation of study
drug, or anticipated need of corticosteroids exceeding prednisone 20 mg/day or
equivalent during the trial, or any other immunosuppressive therapy within 4 weeks
prior to study entry.
12. Virological tests: Hepatitis B virus surface antigen (HBsAg) positive and/or
hepatitis B core antibody (HBcAb) positive, and hepatitis B virus (HBV)
deoxyribonucleic acid (DNA)>ULN of the testing agency; Hepatitis C antibody (HCV-Ab)
positive and hepatitis C virus-RNA (HCV-RNA)>ULN of the testing agency; Anti-human
immunodeficiency virus (Anti-HIV) positive. Participants will be excluded from the
study if any of the above criteria is met.
13. Uncontrolled active infections requiring oral or intravenous systemic therapy,
except for local treatment.
14. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
drainage (once a month or more frequently).
15. Pregnant or lactating women.
16. Known mental disorder that may affect study compliance or poor compliance.
17. Other serious systemic diseases or laboratory abnormalities or other reasons that
the investigator believes are not appropriate for participating in the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Sun Yat-sen Memorial Hospital
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Recruiting
Contact:
Last name:
Danian Nie
Facility:
Name:
Sun Yat-sen University Cancer Center
Address:
City:
Guangzhou
Zip:
510000
Country:
China
Status:
Recruiting
Contact:
Last name:
Yang Liang, MD
Facility:
Name:
Guangdong Provincial People's Hospital
Address:
City:
Guangzhou
Zip:
510080
Country:
China
Status:
Recruiting
Contact:
Last name:
Peilong Lai, MD
Facility:
Name:
The Affiliated Hospital of Guizhou Medical University
Address:
City:
Guiyang
Zip:
550004
Country:
China
Status:
Recruiting
Contact:
Last name:
Jishi Wang, MD
Facility:
Name:
Henan Provincial People's Hospital
Address:
City:
Zhengzhou
Zip:
450003
Country:
China
Status:
Recruiting
Contact:
Last name:
Zunmin Zhu, MD
Facility:
Name:
The Affiliated Hospital of Xuzhou Medical University
Address:
City:
Xuzhou
Zip:
221000
Country:
China
Status:
Recruiting
Contact:
Last name:
Zhenyu Li, MD
Facility:
Name:
The First Affiliated Hospital of Nanchang University
Address:
City:
Nanchang
Zip:
330006
Country:
China
Status:
Recruiting
Contact:
Last name:
Fei Li, MD
Facility:
Name:
The First Hospital of Jilin University
Address:
City:
Changchun
Zip:
130021
Country:
China
Status:
Recruiting
Contact:
Last name:
Sujun Gao, MD
Facility:
Name:
Affiliated Zhongshan Hospital of Dalian University
Address:
City:
Dalian
Zip:
116001
Country:
China
Status:
Recruiting
Contact:
Last name:
Meiyun Fang, MD
Contact backup:
Last name:
Xiang Li
Facility:
Name:
Shengjing Hospital of China Medical University
Address:
City:
Shenyang
Zip:
110000
Country:
China
Status:
Recruiting
Contact:
Last name:
Wei Yang, MD
Facility:
Name:
The Second Affiliated Hospital of Kunming Medical University
Address:
City:
Kunming
Zip:
650033
Country:
China
Status:
Recruiting
Contact:
Last name:
Zeping Zhou, MD
Facility:
Name:
The First Affiliated Hospital, Zhejiang University School of Medicine
Address:
City:
Hangzhou
Zip:
310003
Country:
China
Status:
Recruiting
Contact:
Last name:
Jie Jin, MD
Phone:
+86-0571-87236898
Email:
jiej0503@163.com
Start date:
September 25, 2024
Completion date:
June 30, 2027
Lead sponsor:
Agency:
Excyte Biopharma Ltd
Agency class:
Industry
Source:
Excyte Biopharma Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06580301
