Recurrent Adult Acute Myeloid LeukemiaPhase 1ARMYNCT02353143
Study of MEN1112 Intravenous Infusion in Relapsed or Refractory Acute Myeloid Leukemia
A Phase 1 study testing MEN1112 in people with Recurrent Adult Acute Myeloid Leukemia and Acute Myeloid Leukemia, in Relapse, run by Menarini Group at 29 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Adult Acute Myeloid Leukemia, Acute Myeloid Leukemia, in Relapse
- What is being tested?
- MEN1112
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 29 sitesin 5 countries
- Study dates
- Dec 2014to 9 Apr 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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; hydroxyurea is allowed to lower WBC count.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at Visit1/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
Who cannot join
- 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.
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- 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).
Trial locations and contacts
29 sites in 5 countries.
29 sites in 5 countries
France9 sites
Study site
Grenoble
Study site
Lille, 59037
Study site
Lyon, 69495
Study site
Marseille, 13273
Study site
Nantes, 44093
Study site
Paris
Study site
Pierre-Bénite
Study site
Toulouse, 31059
Study site
Villejuif, 94805
Spain6 sites
Study site
Badalona, 08916
Study site
Barcelona, 08035
Study site
Pamplona
Study site
Salamanca
Study site
Seville
Study site
Valencia, 46026
Belgium5 sites
Study site
Antwerp, 2060
Study site
Brussels, 1200
Study site
Liège, 4000
Study site
Roeselare
Study site
Yvoir, 5530
Italy5 sites
Study site
Bologna, 40126
Study site
Brescia, 25123
Study site
Milan, 20132
Study site
Rome, 00133
Study site
Torino, 10126
Germany4 sites
Study site
Dresden
Study site
Essen, 45147
Study site
Frankfurt, 60590
Study site
Munich, 81377
About this study
Official title: First in Man Study With MEN1112, a CD157 Targeted Monoclonal Antibody, in Relapsed or Refractory Acute Myeloid Leukemia.
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.
Read the detailed 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 for two 21-day cycles.
Approximately 100 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. 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 four-week End of Treatment period and a Follow-up period. In Step 1 and Step 2, DLT and MTD will be assessed when MEN1112 is given as a 'one shot' infusion (first group of patients) for all doses as well as a 'ramp up' administration to be infused in 3 days for the first two doses in Cycle 1 (second group of patients).
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 approx. 40 planned visits at site, including Screening,Treatment, End of Treatment, Follow-up period and the End of Study visit.
- Being tested
- MEN1112
- Keywords
- Acute Myeloid Leukemia, AML, Relapsed, Refractory, MEN1112, Monoclonal antibody
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEN1112Drug
Intravenous infusion of MEN1112 pro/Kg body weight dose will be administered for two 21-day cycles; MEN1112 dose is administered as' one shot infusion' (first group of patients) and as a dose to be infused in 3 days for the first two doses in Cycle 1 (second group of patients).
Two treatment cycles will be followed by a 4-week End of Treatment Period and a Follow-up period. 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).
| Study group | Role | What they receive |
|---|---|---|
| MEN1112 | Experimental | Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation Receives: Drug: MEN1112 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity (DLT)
Identification of DLT defined as an adverse event occurring during the first treatment cycle, judged to be related to MEN1112 and meeting any of the following criteria:
- Grade 3 non-haematological toxicity lasting more than 7 days
- Grade ≥ 4 non-haematological toxicity.
Measured: over 3 weeks after the first dose
Maximum Tolerated Dose (MTD)
Identification of MTD defined as one dose level below the Maximum Administered Dose (i.e. one dose level below the one at which ≥ 2 DLTs out of 6 treated patients occur).
Measured: over 3 weeks after the first dose
Secondary outcomes (8)
Treatment Emergent Signs and Symptoms (TESSs)
Number of patients with Treatment Emergent Signs and Symptoms (TESSs) by CTCAE severity grade >3 and treatment related causality
Measured: 6 months
MEN1112 Pharmacokinetic (PK) Parameter Cmax
Cmax is the maximum serum drug concentration. For Cohort 1 to 3c (administration as 'one shot' infusion) Cmax is measured at the end of the first intravenous infusion ( 1 to 6 hours; depending on the individual subjects being the infusion frequently interrupted) For Cohort 1.7, 2.0 and 3.0 (dose administration as ramp up, divided in three sub-doses), Cmax is measured at the end of each out of 3 intravenous infusions
Measured: end of intravenous infusion
MEN1112 PK Parameter AUC (0-t)
AUC (0-t) is the area under the serum concentration-time curve from time 0 extrapolated to t time evaluated after the first dose
Measured: Dose 1- cycle 1
MEN1112 PK Parameter AUC (0-∞)
AUC (0-∞) is the area under the serum concentration-time curve from time 0 extrapolated to infinite time
Measured: dose 1 of cycle 1
MEN1112 PK Parameter t1/2
t1/2 is the drug elimination half-life
It is calculated on the first dose for all cohorts
Measured: dose 1 of cycle 1
Complete Remission (CR) Rate
CR rate at any time point, where CR is defined as: bone marrow blasts <5%, absence of extramedullary disease, absolute neutrophil count >1 x 109/L and platelet count > 100 x 109/L.
According to the protocol, the efficacy analysis population includes all patients completing the first treatment cycle and having a post-cycle peripheral blood lab test and bone marrow aspirate.
Measured: 6 months
Best Response Rate
best observed response at any time point to include Complete Remission (CR is defined as bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 x 109 / L and platelet count > 100 x 109 / L) Complete Remission with incomplete blood count recovery [CRi defined as all criteria for CR except residual thrombocytopenia (platelets <100 x 109/L), and/or neutropenia (absolute neutrophil count <1 x 109/L)] Partial remission (PR defined as all haematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50%.
Measured: 6 months
Overall Survival
Overall Survival (OS) is the time from the date of the first drug administration to the date of death from any cause. If the fatal event does not occur during the study, the overall survival time is censored at the date when the patient was last known to be alive.
The overall survival (OS) is calculated on 29 patients (72.5%) out of 40 belonging to the efficacy population.
Results are reported as mean (and range) days
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2015 (estimated)
- Study startDec 2014
- Primary completion9 Apr 2021
- Study completion9 Apr 2021
Why it stopped: The Sponsor accepted the iDSMB recommendation to terminate the study due to evidence of unpredictable liver toxicity and meaningful target engagement not translating into any clinical objective response.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Adult Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- The study included ascending doses in the range 0.1 mg/kg to 2.5 mg/kg. According to the Data Safety Review Board, doses to be sequentially tested are 0.1, 0.3, 0.6, 1, 1.7, 2.5 mg/kg single shot and 1.7, 2, and 3 mg/kg ramp up
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menarini Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Adriano Venditti, Professor, MD, Study chair, Hematology Department, "Tor Vergata" University Viale Oxford, 81 00133 Rome, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02353143
- Sponsor's protocol ID
- ARMY-1
- Other IDs
- 2014-002433-59, 2014
- Acronym
- ARMY
- Status last verified
- Mar 2024
- First submitted
- 14 Jan 2015
- Last updated
- 12 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First in Man Study With MEN1112, a CD157 Targeted Monoclonal Antibody, in Relapsed or Refractory Acute Myeloid Leukemia.
- ClinicalTrials.gov ID
- NCT02353143
- Acronym / sponsor ID
- ARMY / ARMY-1
- Keywords
- Acute Myeloid Leukemia, AML, Relapsed, Refractory, MEN1112, Monoclonal antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Sponsor accepted the iDSMB recommendation to terminate the study due to evidence of unpredictable liver toxicity and meaningful target engagement not translating into any clinical objective response.
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Menarini GroupIndustry (pharma, biotech, devices)
- Study start
- Dec 2014 (actual)
- Primary completion
- 9 Apr 2021 (actual)
- Study completion
- 9 Apr 2021 (actual)
- First posted
- 2 Feb 2015 (estimated)
- Results
- Posted 12 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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 for two 21-day cycles.
Approximately 100 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. 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 four-week End of Treatment period and a Follow-up period. In Step 1 and Step 2, DLT and MTD will be assessed when MEN1112 is given as a 'one shot' infusion (first group of patients) for all doses as well as a 'ramp up' administration to be infused in 3 days for the first two doses in Cycle 1 (second group of patients).
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 approx. 40 planned visits at site, including Screening,Treatment, End of Treatment, Follow-up period and the End of Study visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study included ascending doses in the range 0.1 mg/kg to 2.5 mg/kg. According to the Data Safety Review Board, doses to be sequentially tested are 0.1, 0.3, 0.6, 1, 1.7, 2.5 mg/kg single shot and 1.7, 2, and 3 mg/kg ramp up
| Arm | Type | Receives |
|---|---|---|
| MEN1112 | Experimental | Drug: MEN1112Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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; hydroxyurea is allowed to lower WBC count.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 at Visit1/Day 1.
- Life expectancy of at least 2 months.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEN1112Intravenous infusion of MEN1112 pro/Kg body weight dose will be administered for two 21-day cycles; MEN1112 dose is administered as' one shot infusion' (first group of patients) and as a dose to be infused in 3 days for the first two doses in Cycle 1 (second group of patients). Two treatment cycles will be followed by a 4-week End of Treatment Period and a Follow-up period. 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). | Drug | MEN1112 |
Primary outcome
Dose Limiting Toxicity (DLT)
Time frame: over 3 weeks after the first dose
Identification of DLT defined as an adverse event occurring during the first treatment cycle, judged to be related to MEN1112 and meeting any of the following criteria: * Grade 3 non-haematological toxicity lasting more than 7 days * Grade ≥ 4 non-haematological toxicity.
Maximum Tolerated Dose (MTD)
Time frame: over 3 weeks after the first dose
Identification of MTD defined as one dose level below the Maximum Administered Dose (i.e. one dose level below the one at which ≥ 2 DLTs out of 6 treated patients occur).
8 secondary outcomes
Treatment Emergent Signs and Symptoms (TESSs)
Time frame: 6 months
MEN1112 Pharmacokinetic (PK) Parameter Cmax
Time frame: end of intravenous infusion
MEN1112 PK Parameter AUC (0-t)
Time frame: Dose 1- cycle 1
MEN1112 PK Parameter AUC (0-∞)
Time frame: dose 1 of cycle 1
MEN1112 PK Parameter t1/2
Time frame: dose 1 of cycle 1
Complete Remission (CR) Rate
Time frame: 6 months
Best Response Rate
Time frame: 6 months
Overall Survival
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adriano Venditti, Professor, MD study chair
Hematology Department, "Tor Vergata" University Viale Oxford, 81 00133 Rome, Italy
29 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MEN1112 in people with Recurrent Adult Acute Myeloid Leukemia and Acute Myeloid Leukemia, in Relapse, run by Menarini Group at 29 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in France, Spain, Belgium, Italy, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (DLT) (time frame: over 3 weeks after the first dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2024.