CD123+ AML/HR-MDS
Conditions
Interventions
Dosing Group:AZD9829
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Participant must be >= 18 years of age at the time of signing the informed consent, including participant reported outcome measures; 2.Participant with hematological malignancy with positive CD123 expression based on flow cytometry or immunohistochemistry by local laboratory; 3.Male and/or female: Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies; 4.Capable of giving signed informed consent as described in Appendix A 3 which includes compliance with the requirements and restrictions listed in the ICF and in this protocol; 5.Willing and able to participate in all required evaluations and procedures in this study protocol including receiving IV administration of study treatment and being admitted, when required, for at least 24 hours during the study treatment administration; 6.ECOG performance status of = 5% BM blasts at time of inclusion;(c).Had at least 1 prior line of therapy for the treatment of current histology, and have no available treatment options. (d) MDS participants who relapsed after allogenic stem cell transplant can be enrolled, including HMA-naïve participants. MDS participants who relapsed after receiving only immunosuppressive therapies, immunomodulatory drugs or any lower-risk MDS therapies (ie, erythropoietin analogues, luspatercerpt, etc.) are excluded. (e) Participants with previous allogeneic stem cell transplant are allowed if they do not have active GVHD, and have been off systemic GVHD treatment for at least 4 weeks before the start of study drug. (f) R/R HR-MDS participants who relapsed after or during HMA should have received at least 4 cycles of HMA or clear progression after the first 2 cycles may enroll to dose escalation phase. (g) R/R HR-MDS participants intolerant to HMA therapy without any other SoC option are allowed to enroll into the dose escalation phase. 9.Participant with R/R AML or R/R HR-MDS, with positive CD123 expression based on flow cytometry or immunohistochemistry by local laboratory; 10.White blood cell counts <= 10,000 cells/mm3 (10 × 10^9/L); use of leukapheresis or hydroxyurea before initiation of study treatment is allowed to achieve this entry.
Exclusion criteria
Exclusion criteria: 1.Serologic status reflecting active hepatitis B or C: (1) Participants who test positive for anti-HBc IgG will need to have a negative HBV PCR result before enrollment. Those who are HBV surface antigen positive and those with detectable HBV using PCR will be excluded. (2) Participants who are HCV antibody positive will need to have a negative PCR result before enrollment. Those who are HCV PCR positive will be excluded; 2.Known to have tested positive for HIV; 3.Cardiovascular disorder defined as: (1).History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia within 6 months prior to start of study treatment. Participants with atrial fibrillation controlled by medication are permitted;(2).Uncontrolled hypertension; (3).Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months; (4).History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening; (5).Symptomatic heart failure (as defined by New York Heart Association class >= 2); (6)Prior or current cardiomyopathy that is not adequately controlled; (7).Severe valvular heart disease; (8).Mean resting QTcF > 470 msec obtained from triplicate ECGs and averaged, recorded within 5 minutes. (i) Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as symptomatic heart failure, congenital LQTS, family history of LQTS or unexplained sudden death under 40 years of age. (j) Concomitant medications known to prolong QTc cannot be used starting with the first dose of study treatment and through the DLT review period (if applicable) or during the scheduled ECG assessments; they can otherwise be used with caution. 4.Known active CMV infection (positive CMV IgM and/or positive PCR result); 5.History of QT prolongation associated with other medications that required discontinuation of that medication; 6.Any unresolved non-hematological toxicity from prior anticancer therapy of CTCAE Grade > 2 with the exception of alopecia, vitiligo, and endocrine disorders that are controlled with replacement hormone therapy; 7.History of another primary malignancy, except for: (a) Malignancy treated with curative intent and with no known active disease for at least 2 years before the first dose of study treatment and with low potential risk for recurrence. Participants with no known active disease for at least 2 years prior to first dose of study treatment who are on maintenance therapy (eg, lenalidomide for multiple myeloma, hormonal maintenance therapy for breast cancer) may be allowed after discussion with the medical monitor. (b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. (c) Adequately treated carcinoma in situ without evidence of disease. (d) Locally non-invasive primary under surveillance or controlled under hormonal therapy (eg, basal cell carcinoma of the skin or prostate cancer under observation or hormone therapy). 8.As judged by the investigator, any evidence of any of the following: (a) severe or uncontrolled systemic disease (including but not limited to serious chronic gas
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of DLTs.;Incidence, severity, and relationship to IMP of AEs, SAEs;abnormal laboratory evaluations;abnormal vital signs;abnormal physical examinations;abnormal ECG results; | — |
Secondary
| Measure | Time frame |
|---|---|
| Plasma concentrations;Pharmacokinetics;Overall response rate;Composite complete response rate;"Complete Remission Complete Remission with Hematologic Incomplete Recovery" rate;Complete response rate;Duration of remission;Time to remission;The percentage of participants who develop ADA;Time to the next treatment;Progression-free survival;Overall survival;Event-free survival;The number of participants who develop ADA; | — |
Countries
China
Contacts
Public ContactJianxiang Wang
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
Outcome results
None listed