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A Phase III placebo-controlled efficacy and safety study of mocravimod as an adjunctive and maintenance treatment in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantatio

Phase 3
Conditions
Acute myeloid leukemia
Cancer
Registration Number
ISRCTN12632431
Lead Sponsor
Priothera S.A.S.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Ongoing
Sex
All
Target Recruitment
249
Inclusion Criteria

Current inclusion criteria:
1. Subjects with a diagnosis of AML (excluding acute promyelocytic leukemia) according to the World Health Organization (WHO) 2022 classification of AML and related precursor neoplasms, including AML with myelodysplasia-related gene mutations.
2. Subjects with European LeukemiaNet (ELN) high-risk or intermediate-risk AML in CR1, intermediate-risk AML in CR1, or AML of any risk in CR2. (Complete remission with incomplete count recovery [CRi] is also allowable).
3. Subjects planned to undergo allogeneic HCT
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

Previous inclusion criteria:
1. Subjects with a diagnosis of AML (excluding acute promyelocytic leukemia) according to the World Health Organization (WHO) 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 European LeukemiaNet (ELN) high risk AML in CR1, intermediate-risk AML in CR1 if MRDpos, or AML of any risk in CR2. Complete remission is defined as: <5% marrow blasts by morphologic examination and no circulating peripheral blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count =1.0 x 10e9/L (1000/µl); platelet count =100 x 10e9/L (100 000/µl)
3. Subjects planned to undergo allogeneic HSCT
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

Exclusion Criteria

Current exclusion criteria as of 19/07/2024:
1. Planned use of anti-thymocyte globulin (ATG), alemtuzumab, 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. Require treatments for cardiac dysfunction
7. Subjects with acute promyelocytic leukemia
8. Blast crisis of chronic myeloid leukemia
9. Cardiac dysfunction
10. Pulmonary dysfunction
11. 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
12. Renal dysfunction with creatinine clearance <45 ml/min by the Cockcroft-Gault formula
13. History of stroke or intracranial hemorrhage within 1 year prior to screening
14. 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

Previous exclusion criteria:
1. Planned use of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide, sirolimus, mycophenolate mofetil, abatacept, or any approved or non-approved medication other than MTX plus CsA or MTX plus TAC 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 HSCT 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. Require treatments for cardiac dysfunction
7. Subjects with acute promyelocytic leukemia
8. Blast crisis of chronic myeloid leukemia
9. Cardiac dysfunction
10. Pulmonary dysfunction
11. 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
12. Renal dysfunction with creatinine clearance <60 ml/min by the Cockcroft-Gault formula
13. History of stroke or intracranial hemorrhage within 1 year prior to screening
14. 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 HSCT

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Relapse-free survival (RFS) measured using patients' medical records at 12 months
Secondary Outcome Measures
NameTimeMethod
Overall survival (OS) measured using patients' medical records at 24 months
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