Study of MEN1112 Intravenous Infusion in Relapsed or Refractory Acute Myeloid Leukemia

NCT02353143 | Terminated Phase 1 Results DMC

• 2 other identifiers: ARMY-12014-002433-59
• Study Type: interventional
• Target: 71
• Locations: 5 countries
• Sites: 29

Brief 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.

Conditions

Recurrent Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia, in Relapse

Keywords

Acute Myeloid Leukemia; AML; Relapsed; Refractory; MEN1112; Monoclonal antibody

Outcome Measures

Primary Outcomes (2)

• 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.

  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).

  over 3 weeks after the first dose

Secondary Outcomes (8)

• Treatment Emergent Signs and Symptoms (TESSs)

  6 months

• MEN1112 Pharmacokinetic (PK) Parameter Cmax

  end of intravenous infusion

• MEN1112 PK Parameter AUC (0-t)

  Dose 1- cycle 1

• MEN1112 PK Parameter AUC (0-∞)

  dose 1 of cycle 1

• MEN1112 PK Parameter t1/2

  dose 1 of cycle 1

Other Outcomes (1)

• Immunogenicity of MEN1112

  64 days

Study Arms (1)

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

Drug: MEN1112

Interventions

MEN1112 DRUG

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).

MEN1112

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Menarini Group: lead

Study Sites (29)

Unknown Facility

Antwerp, 2060, Belgium

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Brussels, 1200, Belgium

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Liège, 4000, Belgium

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Roeselare, Belgium

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Yvoir, 5530, Belgium

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Grenoble, France

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Lille, 59037, France

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Lyon, 69495, France

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Marseille, 13273, France

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Nantes, 44093, France

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Paris, France

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Pierre-Bénite, France

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Toulouse, 31059, France

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Villejuif, 94805, France

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Dresden, Germany

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Essen, 45147, Germany

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Frankfurt, 60590, Germany

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Munich, 81377, Germany

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Bologna, 40126, Italy

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Brescia, 25123, Italy

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Milan, 20132, Italy

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Rome, 00133, Italy

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Torino, 10126, Italy

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Badalona, 08916, Spain

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Barcelona, 08035, Spain

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Pamplona, Spain

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Salamanca, Spain

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Seville, Spain

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Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Study terminated due to any clinical objective response observed in the patients' study population and under the study procedures implemented in the trial

Results Point of Contact

• Title: Director of Clinical Sciences
• Organization: Menarini Ricerche

acapriati@menarini-ricerche.it

003905556809990

Study Officials

• Adriano Venditti, Professor, MD

  Hematology Department, "Tor Vergata" University Viale Oxford, 81 00133 Rome, Italy

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 14, 2015
• First Posted: February 2, 2015
• Study Start: December 1, 2014
• Primary Completion: April 9, 2021
• Study Completion: April 9, 2021
• Last Updated: August 12, 2024
• Results First Posted: August 12, 2024

Record last verified: 2024-03

Locations

FR (9); DE (4); BE (5); ES (6); IT (5)