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JAPANESE
国立保健医療科学院
JRCT ID: jRCT2011230008

Registered date:26/05/2023

Mocravimod as Adjunctive and Maintenance Treatment in AML Patients Undergoing Allo-HCT

Basic Information

Recruitment status Recruiting
Health condition(s) or Problem(s) studiedAacute myeloid leukemia (AML)
Date of first enrollment13/02/2024
Target sample size30
Countries of recruitmentFrance,Japan,Germany,Japan,Israel,Japan,Italy,Japan,Poland,Japan,Romania,Japan,Spain,Japan,Switzerland,Japan,Taiwan,Japan,United Kingdom,Japan,United States,Japan,Brazil,Japan,Argentina,Japan
Study typeInterventional
Intervention(s)i) 1 mg arm 1 mg/day mocravimod: subjects will receive 1 mg of mocravimod orally once per day from Cycle 1 Day 1 for 12 cycles post first IMP intake ii) 3 mg arm 3 mg/day mocravimod: subjects will receive 3 mg of mocravimod orally once per day from Cycle 1 Day 1 for 12 cycles post first IMP intake iii) Placebo arm Placebo: subjects will receive placebo orally once per day from Cycle 1 Day 1 for 12 cycles post first IMP intake - Randomization to mocravimod 1 mg, mocravimod 3 mg, or matching placebo will be in a 1:1:1 ratio

Outcome(s)

Primary OutcomeRelapse-Free Survival (RFS) To compare the efficacy of mocravimod to that of placebo
Secondary OutcomeOverall Survival (OS) To compare mocravimod's effect on OS to that of placebo

Key inclusion & exclusion criteria

Age minimum>= 18age old
Age maximum<= 75age old
GenderBoth
Include criteria1. Subjects with a diagnosis of AML (excluding acute promyelocytic leukemia) according to the World Health Organization (WHO) 2022 classification of AML 2. Subjects with European LeukemiaNet (ELN) high-risk AML in CR1, intermediate-risk AML in CR1, or AML of any risk in CR2 3. Subjects planned to undergo allogeneic HCT, with all of the following parameters met: - Planned use of fully matched related or unrelated donor or with no more than 1 antigen mismatch at human leukocyte antigen (HLA)-A, -B, -C, -DRB1 or -DQB1 locus for either related or unrelated donor. - Planned use of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) - Planned use of myeloablative conditioning regimen that is expected to result in donor chimerism of >= 90% - Planned use of CsA-based or TAC-based GvHD prophylaxis 4. Life expectancy >= 6 months at screening 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Male or female, age >= 18 years and <= 75 years 7. Body weight of >= 50 kg 8. Able and willing to provide written informed consent and comply with the trial protocol and procedures 9. Contraception for females of childbearing potential and sexually active males 10. Affiliation to a national health insurance scheme (only applicable if required by local regulations)
Exclude criteria1. Planned use of anti-thymocyte globulin (ATG), alemtuzumab, sirolimus, abatacept, for GvHD prophylaxis. 2. Planned use of serotherapy during conditioning, including ATG and alemtuzumab. 3. Planned ex vivo major graft manipulation, including T-cell depletion or CD34+ selection. 4. Subjects having received prior allogeneic HCT or recipients of a solid organ transplant. 5. Immunosuppressive drugs for concomitant disease. Subjects must be able to be off prednisone (> 10 mg/day) or other immunosuppressive medications for at least 3 days prior to the start of treatment of the study. Physiologic replacement dosing of hydrocortisone is permissible. 6. Major surgery within 4 weeks prior to randomization or a major wound that has not fully healed. 7. Require any of the following treatments for cardiac dysfunction: - Treatment with medication that impairs cardiac conduction (e.g. beta blockers, verapamil-type and diltiazem-type calcium channel blockers, or cardiac glycosides) - Treatment with quinidine 8. Subjects with acute promyelocytic leukemia. 9. Diagnosis of any previous or concomitant malignancy, except subjects diagnosed with localized basal cell carcinoma of the skin or in situ cervical cancer, or subjects who have completed treatment (chemotherapy and/or surgery and/or radiotherapy) with curative intent for the malignancy at least 3 years prior to enrollment. 10. Blast crisis of chronic myeloid leukemia. 11. Concurrent severe and/or uncontrolled medical condition including: - Clinically significant pulmonary fibrosis - Tuberculosis, except for history of successfully treated tuberculosis or history of prophylactic treatment after positive purified protein derivative (PPD) skin reaction - Subjects with any other types of clinically significant obstructive pulmonary disease - Uncontrolled diabetes mellitus as assessed by the investigator or diabetes complicated with organ involvement such as diabetic nephropathy or retinopathy - Uncontrolled seizure disorder - Uncontrolled depression or history of suicide attempts/ideation 12. Cardiac dysfunction as defined by: - Myocardial infarction within the last 3 months of trial entry - Reduced left ventricular function with an ejection fraction < 40% within 6 weeks before signing informed consent - History or presence of stable or unstable ischemic heart disease (IHD), myocarditis, or cardiomyopathy - New York Heart Association (NYHA) Class II-IV congestive heart failure - Unstable cardiac arrhythmias including history of or presence of symptomatic bradycardia - Resting heart rate (physical exam or 12-lead electrocardiogram (ECG)) < 50 bpm - History or current diagnosis of ECG abnormalities indicating significant risk of safety such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, presence of a clinically relevant impairment of cardiac conduction including sick sinus syndrome, or sino-atrial heart block, clinically significant atrioventricular (AV) block, bundle branch block or resting QTc (Fridericia preferred, but Bazett acceptable) > 450 msec for males and > 470 msec for females at Screening or Baseline ECG - History or presence of symptomatic arrhythmia or arrhythmia requiring treatment or being otherwise of clinical significance - Uncontrolled arterial hypertension; if controlled, the medication must be stable for 3 months prior to baseline visit - Requiring treatment with prohibited medication listed under 'Exclusion criteria - prior/concomitant therapy' - History of syncope of suspected cardiac origin - History of familial long QT syndrome or known family history of Torsades de Pointes 13. Pulmonary dysfunction as defined by oxygen saturation < 90% on room air. Pulmonary function test (PFT) is required only in the case of symptomatic or prior known impairments within 6 weeks before signing informed consent. If PFTs are performed, corrected diffusing capacity of the lung for carbon monoxide (DLCO) < 50% and forced expiratory volume in 1 second (FEV1) < 50% predicted are exclusionary. 14. Significant liver disease or liver injury or known history of alcohol abuse, chronic liver or biliary disease. Hepatic dysfunction as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN); or total bilirubin > 1.5 x ULN 15. Renal dysfunction with creatinine clearance < 60 mL/min by the Cockcroft-Gault formula. 16. History of stroke or intracranial hemorrhage within 1 year prior to screening. 17. Active clinically significant infection (viral, bacterial, or fungal) that requires ongoing antimicrobial therapy and in the judgment of the investigator represents a risk to proceeding with HCT. 18. History of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) defined as a positive HIV antibody, hepatitis B surface antigen (HBsAg) or hepatitis C antigen. 19. Subjects who are breastfeeding or have positive pregnancy test (serum pregnancy test is mandatory at screening and prior to the IMP administration on Cycle 1 Day 1 for women of childbearing potential). 20. Known allergy to any of the components of mocravimod (e.g. excipient) and any other medications that are not study related but will be used according to local SoC, such as conditioning regimen agents, GvHD prophylaxis, and concomitant medications and therapies. 21. Diagnosis of macular edema during screening. Subjects with a history of macular edema will be allowed to enter the study provided they do not have macular edema at the ophthalmic examination at screening. 22. Participation in another interventional clinical trial within 4 weeks prior to randomization or participation in a concomitant interventional clinical trial. Other Exclusions 23. Any other condition that, in the opinion of the investigator, makes the subject ineligible for the study. 24. Subjects under legal protection measure (guardianship, trusteeship, or safeguard of justice) and/or inability or unwillingness to comply with the requirements and procedures of this trial

Related Information

Contact

Public contact
Name Clinical trial contact
Address Kyutaromachi 4-chome 1-3, Chuo-ku, Osaka city, Osaka 541-0056, Japan Osaka Japan 541-0056
Telephone +81-6-4560-2001
E-mail ICONCR-Chiken@iconplc.com
Affiliation ICON Clinical Research GK
Scientific contact
Name Elisabeth Kueenburg
Address 57 Avenue General de Gaulle, Saint Louis, 68300 France Japan 68300
Telephone 33-3-67510040
E-mail elisabeth.kueenburg@priothera.com
Affiliation Priothera S.A.S.