Conditions recurrent adult acute myeloid leukemia, acute myeloid leukemia, in relapse
Treatment men1112
Phase phase 1
Sponsor Menarini Group
Start date December 2014
End date September 2017
Trial size 50 participants
Trial identifier NCT02353143, 2014-002433-59, ARMY-1


The purpose of this study is to assess the safety of MEN1112, given as intravenous infusion, in patients with relapsed or refractory AML. Pharmacokinetics, clinical activity and potential immunogenicity of MEN1112 will be evaluated as well.

Recruiting in the following locations…

United States No locations recruiting
Other countries Spain

Study Design

Intervention model single group assignment
Primary purpose treatment
Masking no masking
Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation
Intravenous infusion of MEN1112 pro/Kg body weight dose on days 1, 8, 15 of a 21-day cycle. Two induction cycles followed by a 3 week End of induction period. Post-induction/Maintenance Visits every 4 weeks with or without maintenance treatment administration, whilst clinical benefit is maintained as per Investigator's judgement. The individual treatment/observation period is six months (except for female patients of childbearing potential that will undergo monthly pregnancy test until 6 months from the last study drug administration).

Primary Outcomes

Dose limiting toxicity (DLT)
time frame: over 3 weeks after the first dose
Maximum tolerated dose (MTD)
time frame: over 3 weeks after the first dose

Secondary Outcomes

Treatment Emergent Signs and Symptoms (TESSs)
time frame: 6 months
MEN1112 Pharmacokinetic (PK) parameter AUC0-∞
time frame: Estimated maximum time frame: 4 weeks
MEN1112 PK parameter Cmax
time frame: Estimated maximum time frame: 4 weeks
MEN1112 PK parameter t1/2
time frame: Estimated maximum time frame: 4 weeks
Complete remission (CR) rate
time frame: 6 months
Best response rate
time frame: 6 months
Overall survival
time frame: 6 months

Eligibility Criteria

All participants at least 18 years old.

Inclusion Criteria: - Male or female patients aged ≥ 18 years. - Documented definitive diagnosis of AML (according to WHO criteria, 2008) that is relapsed/refractory to standard treatment, for which no standard therapy is available or the patient refuses standard therapy. - WBC count ≤ 10 x 109/L at Visit 1 (Day 1); hydroyxurea is allowed to lower WBC count. - Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at Visit 1 (Day 1). - Life expectancy of at least 2 months. - Adequate renal and hepatic laboratory assessments: Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic organ involvement, Total Bilirubin ≤2.0 × ULN, Serum creatinine ≤2.0 × ULN. - Able to give written informed consent before any study related procedure Exclusion Criteria: - Acute promyelocytic leukaemia (French-American-British M3 classification). - Active central nervous system involvement. - Haematopoietic stem cell transplantation (HSCT) performed within 3 months prior to Screening Visit. - Active infection requiring intravenous antibiotics. - Life-threatening illnesses other than AML, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety or interfere with the patient's ability to comply with the study activities. - Anti-tumour therapy within 14 days of study Visit 1 (Day 1, excluding hydroxyurea). - Prior participation in an investigational study (procedure or device) within 21 days of study Visit 1 (Day 1). - Radiotherapy within 28 days prior to study Visit 1 (Day 1) or scheduled along the study conduct. - Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). - Other active malignancies. History of malignancy in the last 12 months (except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast or non-melanoma skin cancer).

Additional Information

Official title First in Man Study With MEN1112, a CD157 Targeted Monoclonal Antibody, in Relapsed or Refractory Acute Myeloid Leukemia.
Description This trial is designed as an open label, non randomised, dose escalation and cohort expansion, first administration to human study to be conducted in approximately 20 European sites. The study is aiming to identify the Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD), to assess the pharmacokinetics and to determine the clinical activity and potential immunogenicity of MEN1112, administered as IV infusion given once every week in a 21 days cycle in patients with relapsed/refractory acute myeloid leukemia (AML). Approximately 50 male and female ≥ 18 years-old patients, with a documented diagnosis of relapsed or refractory AML (not M3 FAB subtype), will be treated in the study, which consists of two steps. Step 1 is the dose escalation phase according to a 3+3 patients cohort design.Incremental mg/Kg doses will be tested given at day 1, 8 and 15 of a 21-day cycle. Briefly, MEN1112 doses are to be administered to 3 patients; if no DLT is observed in a cohort of 3 DLT evaluable patients at a given dose level, the next cohort of 3 new patients will be treated with the next higher dose. In case of DLT occurrence by one of the three patients at any dose, the cohort will be expanded to 6 DLT evaluable patients at the same dose level. If two or more patients at a given dose level exhibit DLT, the dose escalation phase will be concluded as the MTD will be identified as one dose level below the one at which ≥ 2 DLT out of 6 treated patients occur. Step 2 is the cohort expansion phase which will include patients treated at the MTD or the maximum dose level judged to be tolerable. In each study Step, patients will be given two induction cycles of MEN1112 followed by a three weeks End of Induction period. Patients will then undergo to 4 post-induction/maintenance visits every 28 days (maintenance administration is allowed in patients who achieve a clinical benefit based on Investigator's judgement) and to an End of Study Visit. Along the study period, adverse events, changes in hematology/serum biochemistry parameters and bone marrow treatment response will represent the major clinical findings to be monitored on regular basis. The individual experimental clinical phase will last up to 6 months (except for female patients of childbearing potential that will undergo monthly pregnancy test until 6 months from the last study drug administration) encompassing 40 planned visits at site, including Screening, Induction, End of Induction, Post-induction/Maintenance and the End of Study visit.
Trial information was received from ClinicalTrials.gov and was last updated in February 2017.
Information provided to ClinicalTrials.gov by Menarini Group.