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A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy

NCT04023526

Description:

The purpose of this study is to determine the efficacy of cusatuzumab in combination with azacitidine in participants with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy
  • Official Title: A Phase 2 Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: CR108609
  • SECONDARY ID: 2019-000473-23
  • SECONDARY ID: 74494550AML2001
  • NCT ID: NCT04023526

Conditions

  • Leukemia, Myeloid, Acute

Interventions

DrugSynonymsArms
AzacitidineAzacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg
CusatuzumabJNJ-74494550Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg

Purpose

The purpose of this study is to determine the efficacy of cusatuzumab in combination with azacitidine in participants with previously untreated acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy.

Detailed Description

      AML is a heterogeneous disease characterized by uncontrolled clonal expansion of
      hematopoietic progenitor cells. As the most common form of acute leukemia, AML accounts for
      the largest number of annual deaths from leukemia. Over 95 percent (%) of AML blasts
      harvested from newly diagnosed AML participants expressed Cluster of Differentiation (CD) 70
      on the cell surface. Cusatuzumab (JNJ‑74494550) is a humanized monoclonal antibody of camelid
      origin, binding with tight affinity to human CD70. Cusatuzumab has been modified to induce
      enhanced antibody-dependent cell-mediated cytotoxicity for therapeutic use in participants
      with cancer. Azacitidine is a pyrimidine nucleoside analogue of cytidine with antineoplastic
      activity and is indicated for the treatment of adult participants with AML or intermediate 2
      and high-risk myelodysplastic syndrome (MDS) with greater than 20% marrow blasts who are not
      eligible for hematopoietic stem cell transplantation. This study will evaluate 2 doses of
      cusatuzumab in combination with standard dose azacitidine in participants with AML who are
      not candidates for intensive chemotherapy (Part 1). Part 1 data will be reviewed by a Data
      Review Committee to select a preferred dose of cusatuzumab. Participants will be enrolled
      into Part 2 at the selected cusatuzumab dose to further evaluate and confirm the response
      rate, other efficacy endpoints, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD).
      The study will include a Screening Phase (28 days prior to randomization), a Treatment Phase,
      and a Follow-up Phase. The study includes evaluations like vital signs, electrocardiogram,
      spirometry test, serum chemistry and hematology tests. The study will be conducted for an
      approximate duration of 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kgExperimentalParticipants will receive azacitidine 75 milligram per meter square (mg/m^2) subcutaneously (SC) or intravenously (IV) on Day 1 through Day 7 and cusatuzumab 10 milligram per kilogram (mg/kg) IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a data review committee (DRC) and when a dose of cusatuzumab is selected, randomization will stop and participants will be enrolled into an expansion cohort (Part 2) to evaluate efficacy.
  • Azacitidine
  • Cusatuzumab
Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kgExperimentalParticipants will receive azacitidine 75 mg/m^2 SC or IV on Day 1 through Day 7 and cusatuzumab 20 mg/kg IV on Day 3 and Day 17 of each 28-day cycle in Part 1. Part 1 findings will be reviewed by a DRC and when a dose of cusatuzumab is selected, randomization will stop and participants will be enrolled into an expansion cohort (Part 2) to evaluate efficacy.
  • Azacitidine
  • Cusatuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Acute myeloid leukemia (AML) according to World Health Organisation (WHO) 2016
             criteria and fulfilling all of the following criteria that defines "not candidates for
             intensive chemotherapy": (a) greater than or equal to (>=)75 years of age or (b)
             Comorbidity of at least one of the following: Eastern Cooperative Oncology Group
             (ECOG) Performance Status of 2; Severe cardiac comorbidity defined as congestive heart
             failure or ejection fraction less than or equal to (<=) 50 percent (%); Severe
             pulmonary comorbidity defined as documented pulmonary disease with lung diffusing
             capacity for carbon monoxide (DLCO) <=65% of expected, or forced expiratory volume in
             1 second (FEV1) <=65% of expected or dyspnea at rest requiring oxygen; Moderate
             hepatic impairment defined according to NCI organ dysfunction classification criteria
             (total bilirubin >=1.5 up to 3 times upper limit of normal [ULN]); Creatinine
             clearance <45 milliliter per minute per 1.73 meter square (mL/ min/1.73 m^2);
             Comorbidity that, in the Investigator's opinion, makes the participant unsuitable for
             intensive chemotherapy and must be documented and approved by the Sponsor before
             randomization; (c) De novo or secondary AML; (d) Previously untreated AML (except:
             emergency leukapheresis, 1 low dose of cytarabine and/or hydroxyurea during the
             screening phase to control hyperleukocytosis but must be discontinued at least one day
             prior to start of azacitidine). All trans retinoic acid (ATRA) treatment for presumed
             acute promyelocytic leukemia is permitted but must be discontinued at least 1 day
             prior to the start of azacitidine; (e) Not eligible for an allogeneic hematopoietic
             stem cell transplantation

          -  ECOG Performance Status score of 0, 1 or 2

        Exclusion Criteria:

          -  Acute promyelocytic leukemia with t (15;17), or its molecular equivalent
             (Promyelocytic leukemia [PML]-Retinoic acid receptor, alpha [RARalpha])

          -  Leukemic involvement or clinical symptoms of leukemic involvement of the central
             nervous system

          -  Use of immune suppressive agents for the past 4 weeks before the first administration
             of cusatuzumab on Cycle 1 Day 1. For regular use of systemic corticosteroids,
             participants may only be included if free of systemic corticosteroids for a minimum of
             5 days before the first administration of cusatuzumab

          -  Prior treatment with a hypomethylating agent for treatment of AML or myelodysplastic
             syndrome (MDS)

          -  A diagnosis of other malignancy that requires concurrent non surgical treatment

          -  Any active untreated systemic infection

          -  Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its
             excipients (that is, mannitol, an excipient of azacitidine)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with Complete Response (CR)
Time Frame:Up to 1.5 years
Safety Issue:
Description:Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.

Secondary Outcome Measures

Measure:Percentage of Participants with CR with Partial Hematological Recovery (CRh)
Time Frame:Up to 1.5 years
Safety Issue:
Description:Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.
Measure:Percentage of Participants with CR plus CRh
Time Frame:Up to 1.5 years
Safety Issue:
Description:Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.
Measure:Percentage of Participants with CR with Incomplete Recovery (CRi)
Time Frame:Up to 1.5 years
Safety Issue:
Description:Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 1.5 years
Safety Issue:
Description:ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.
Measure:Percentage of Participants with CR without MRD
Time Frame:Up to 1.5 years
Safety Issue:
Description:Percentage of participants with CR without minimal residual disease (MRD) will be reported and is defined as less than 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3; determined by central lab).
Measure:Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)
Time Frame:Up to 1.5 years
Safety Issue:
Description:Percentage of participants with negative MRD who achieved CR, CRh, CRi, or MLFS will be reported and is defined as less than (<) 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level <10^-3).
Measure:Time to Response
Time Frame:Up to 1.5 years
Safety Issue:
Description:Time to response is defined as time from randomization to achieving CR/CRi/CRh.
Measure:Duration of Response
Time Frame:Up to 1.4 years
Safety Issue:
Description:Duration of response is defined as time from achieving CR/CRi/CRh to disease relapse.
Measure:Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Up to 1.9 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.
Measure:Minimum Serum Concentration (Cmin) of Cusatuzumab
Time Frame:Up to 1.9 years
Safety Issue:
Description:Cmin is the minimum observed serum concentration.
Measure:Maximum Serum Concentration (Cmax) of Cusatuzumab
Time Frame:Up to 1.9 years
Safety Issue:
Description:Cmax is the maximum observed serum concentration.
Measure:Number of Participants with Anti-cusatuzumab Antibodies
Time Frame:Up to 1.9 years
Safety Issue:
Description:Number of participants exhibiting anti-drug antibodies for cusatuzumab alone and in combination with azacitidine will be reported.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

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