A phase IIb placebo-controlled efficacy and safety study of mocravimod in AML patients undergoing HSCT
- Conditions
- Patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML)MedDRA version: 20.1Level: PTClassification code 10018651Term: Graft versus host diseaseSystem Organ Class: 10021428 - Immune system disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2021-002864-36-FR
- Lead Sponsor
- Priothera S.A.S.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 160
1. Subjects with a diagnosis of AML (excluding acute promyelocytic leukemia) according to the World Health Organization 2016 classification of AML and related precursor neoplasms, including secondary AML after an antecedent hematological disease (e.g. myelodysplastic syndrome) and therapy-related AML.
2. Subjects with ELN high risk AML in CR1 or any other AML in CR2. (Complete remission with incomplete count recovery [CRi] is also allowable).
o Complete remission is defined as leukemia clearance (< 5% marrow blasts and no circulating peripheral blasts) in conjunction with normal values for absolute neutrophil count and platelet count, no extramedullary manifestation of leukemia and no need for repeat blood transfusions.
o CRi is defined as meeting all complete remission criteria except for an absolute neutrophil count < 1,000/µL or platelet count < 100,000/µL.
3. Subjects planned to undergo allogeneic HSCT, with all of the following parameters met:
o Use of fully matched related or unrelated donor (10/10 HLA-matched), and
o Use of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells, and
o Use of protocol-approved (myeloablative) conditioning regimen, and
o Use of CsA and MTX as GVHD prophylaxis
4. Life expectancy = 6 months at screening.
5. Karnofsky Performance Status (KPS) = 70%.
6. Male or female, age = 18 years and = 75 years.
Subjects = 65 years must have a Sorror (hematopoietic cell transplantation-specific comorbidity index [HCT-CI]) Score = 3.
7. Able and willing to provide written informed consent and comply with the trial protocol and procedures.
8. For females of childbearing potential who are sexually active and males who have sexual contact with a female of childbearing potential: willingness to use reliable methods of contraception (oral contraceptives, contraceptive injection, male vasectomy, condom with spermicidal agent, or sexual abstinence).
Contraception is to be used from the Screening visit until the EOT visit, and in any case for at least 6 months after the last dose of IMP.
A female is considered of childbearing potential following menarche and until becoming post-menopausal unless permanently sterile. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks before IMP treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment, she is considered not of childbearing potential.
9. Sexually active males must use a condom during intercourse from the Screening visit until at least 6 months after the last dose of IMP and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the IMP via seminal fluid.
10. Affiliation to a national health insurance scheme (according to applicable local requirements).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 140
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
1.Planned use of tacrolimus, anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide, or mycophenolate mofetil for GVHD prophylaxis.
2.Planned use of serotherapy during conditioning
3.Planned ex vivo major graft manipulation
4.Subjects having received prior allogeneic HSCT or recipients of a solid organ transplant
5.Vaccination within 4 weeks prior to screening
6.Immunosuppressive drugs for concomitant disease. Subjects off prednisone or other immunosuppressive medications <3 days prior study treatment
7.Major surgery within 4weeks prior screening or a major wound, not fully healed
8.Require any of the following treatments for cardiac dysfunction:
-treatment with medication that impairs cardiac conduction
-Concomitant use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
-Treatment with quinidine
9.Subjects with acute promyelocytic leukemia
10.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 with curative intent for the malignancy at least 6 months prior to enrollment
11.Blast crisis of chronic myeloid leukemia
12.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 PPD skin reaction
-Subjects receiving daily therapies for asthma
-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.
13.Cardiac dysfunction as defined by:
-Myocardial infarction within the last 3 months of trial entry
-Reduced left ventricular function with an ejection fraction <40% as measured by MUGA scan or echocardiogram within 6weeks before signing ICF
-History or presence of stable or unstable IHD, myocarditis or cardiomyopathy
-NYHA Class II-IV congestive heart failure
-Unstable cardiac arrhythmias including history of or presence of symptomatic bradycardia
-Resting heart rate ECG <60bpm
-History or current diagnosis of ECG abnormalities indicating significant risk of safety such as: Concomitant clinically significant cardiac arrhythmias, or sino-atrial heart block, clinically significant atrioventricular (AV) block, bundle branch block or resting QTc >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 of clinical significance
-Uncontrolled arterial hypertension; if controlled, the medication must be stable for 3 months prior to baseline
-Requiring treatment with prohibited medication
-History of syncope of suspected cardiac origin
-History of familial long QT syndrome or known family history of Torsades de Pointes
14.Pulmonary dysfunction as defined by oxygen saturation <90% on room air. PFT is required only in the case of symptomatic or prior known impairments within 6weeks before signing ICF -with pulmonary function <50% corrected diffusing capacity of the lung for carbon monoxide (DLCO) and <50% predicted forced expiratory volume in 1 second (FEV1).
15.Significant liver diseas
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess mocravimod’s effect as an adjunctive therapy to HSCT on GVHD and GVL after a 12-month treatment period.;Secondary Objective: To assess mocravimod’s effect on overall survival (OS) at 24 months, following a 12-month treatment and a 12-month follow-up period.;Primary end point(s): Refractory GVHD-free, relapse-free survival (rGRFS) at Month 12 after HSCT;Timepoint(s) of evaluation of this end point: Month 12 after HSCT
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Overall survival (OS) at Month 24 after HSCT;<br>- Relapse-free survival (RFS) at Month 24 after HSCT;<br>- Survival free from refractory acute GVHD (aGVHD) at Month 12 after HSCT;<br>- Survival free from moderate/severe chronic GVHD (cGVHD) at Month 12 and at Month 24 after HSCT;<br>- Non-relapse related mortality at Month 12 and at Month 24 after HSCT;<br>- Cumulative incidence of relapse at Month 12 and at Month 24 after HSCT; <br>- rGRFS at Month 24 after HSCT; <br>;Timepoint(s) of evaluation of this end point: - Month 24 after HSCT;<br>- Month 12 and at Month 24 after HSCT.