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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 (CULMINATE)

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ClinicalTrials.gov Identifier: NCT04023526
Recruitment Status : Recruiting
First Posted : July 17, 2019
Last Update Posted : January 31, 2020
Sponsor:
Collaborator:
argenx BVBA
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Tracking Information
First Submitted Date  ICMJE July 16, 2019
First Posted Date  ICMJE July 17, 2019
Last Update Posted Date January 31, 2020
Actual Study Start Date  ICMJE July 29, 2019
Estimated Primary Completion Date December 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
Percentage of Participants with Complete Response (CR) [ Time Frame: Up to 1.5 years ]
Percentage of participants with complete response based on European Leukemia Network (ELN) 2017 response criteria assessment will be reported.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • Percentage of Participants with CR with Partial Hematological Recovery (CRh) [ Time Frame: Up to 1.5 years ]
    Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.
  • Percentage of Participants with CR plus CRh [ Time Frame: Up to 1.5 years ]
    Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.
  • Percentage of Participants with CR with Incomplete Recovery (CRi) [ Time Frame: Up to 1.5 years ]
    Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.
  • Overall Response Rate (ORR) [ Time Frame: Up to 1.5 years ]
    ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.
  • Percentage of Participants with CR without MRD [ Time Frame: Up to 1.5 years ]
    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).
  • Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS) [ Time Frame: Up to 1.5 years ]
    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).
  • Time to Response [ Time Frame: Up to 1.5 years ]
    Time to response is defined as time from randomization in Part 1 or enrollment in Part 2 to achieving the first response of CR, CRh, or CRi.
  • Duration of Response [ Time Frame: Up to 1.4 years ]
    Duration of response is defined as time from achieving the first response of CR, CRh, or CRi to disease relapse or death from any cause.
  • Red Blood Cell (RBC) or Platelets Transfusion Independence [ Time Frame: Up to 1.5 years ]
    Transfusion independence (RBC or platelets) is defined as a period of at least 56 consecutive days with no transfusion between first dose of study drug and the last dose of study drug +30 days.
  • Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 1.9 years ]
    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.
  • Minimum Serum Concentration (Cmin) of Cusatuzumab [ Time Frame: Up to 1.9 years ]
    Cmin is the minimum observed serum concentration.
  • Maximum Serum Concentration (Cmax) of Cusatuzumab [ Time Frame: Up to 1.9 years ]
    Cmax is the maximum observed serum concentration.
  • Number of Participants with Anti-cusatuzumab Antibodies [ Time Frame: Up to 1.9 years ]
    Number of participants exhibiting anti-drug antibodies for cusatuzumab alone and in combination with azacitidine will be reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
  • Percentage of Participants with CR with Partial Hematological Recovery (CRh) [ Time Frame: Up to 1.5 years ]
    Percentage of participants with CRh will be reported based on ELN 2017 response criteria assessment.
  • Percentage of Participants with CR plus CRh [ Time Frame: Up to 1.5 years ]
    Percentage of participants with CR plus CRh will be reported based on ELN 2017 response criteria assessment.
  • Percentage of Participants with CR with Incomplete Recovery (CRi) [ Time Frame: Up to 1.5 years ]
    Percentage of participants with CRi will be reported based on ELN 2017 response criteria assessment.
  • Overall Response Rate (ORR) [ Time Frame: Up to 1.5 years ]
    ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria assessment.
  • Percentage of Participants with CR without MRD [ Time Frame: Up to 1.5 years ]
    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).
  • Percentage of Participants with Negative MRD who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS) [ Time Frame: Up to 1.5 years ]
    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).
  • Time to Response [ Time Frame: Up to 1.5 years ]
    Time to response is defined as time from randomization to achieving CR/CRi/CRh.
  • Duration of Response [ Time Frame: Up to 1.4 years ]
    Duration of response is defined as time from achieving CR/CRi/CRh to disease relapse.
  • Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 1.9 years ]
    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.
  • Minimum Serum Concentration (Cmin) of Cusatuzumab [ Time Frame: Up to 1.9 years ]
    Cmin is the minimum observed serum concentration.
  • Maximum Serum Concentration (Cmax) of Cusatuzumab [ Time Frame: Up to 1.9 years ]
    Cmax is the maximum observed serum concentration.
  • Number of Participants with Anti-cusatuzumab Antibodies [ Time Frame: Up to 1.9 years ]
    Number of participants exhibiting anti-drug antibodies for cusatuzumab alone and in combination with azacitidine will be reported.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy
Official Title  ICMJE A Phase 2 Study of Cusatuzumab Plus Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy
Brief Summary 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 antibodydependent 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia, Myeloid, Acute
Intervention  ICMJE
  • Drug: Azacitidine
    Azacitidine SC or IV will be administered at a standard dose of 75 mg/m^2 on days 1-7 of each cycle.
  • Drug: Cusatuzumab
    Cusatuzumab IV will be administered as 10 mg/kg or 20 mg/kg.
    Other Name: JNJ-74494550
Study Arms  ICMJE
  • Experimental: Azacitidine 75 mg/m^2 and Cusatuzumab 10 mg/kg
    Participants 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.
    Interventions:
    • Drug: Azacitidine
    • Drug: Cusatuzumab
  • Experimental: Azacitidine 75 mg/m^2 and Cusatuzumab 20 mg/kg
    Participants 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.
    Interventions:
    • Drug: Azacitidine
    • Drug: Cusatuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2019)
150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2021
Estimated Primary Completion Date December 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Acute myeloid leukemia (AML) according to World Health Organisation (WHO) 2016 criteria and fulfilling all of the following criteria that defines those who are "not candidates for intensive chemotherapy":

    1. greater than or equal to (>=)75 years of age or
    2. less than (<) 75 years of age with at least one of the following comorbidities: 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
  • De novo or secondary AML
  • Previously untreated AML (except: emergency leukapheresis, hydroxyurea, and/or 1 dose of cytarabine [example: 1-2 gram per meter square {g/m^2}] during the Screening Phase to control hyperleukocytosis. These treatments must be discontinued >=24 hours prior to start of study drug). Empiric all trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but APL must be ruled out and ATRA must be discontinued >=24 hours prior to the start of study drug
  • Not eligible for an allogeneic hematopoietic stem cell transplantation
  • ECOG Performance Status score of 0, 1 or 2

Exclusion Criteria:

  • Acute promyelocytic leukemia
  • 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 3. 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. Treatment of adrenal insufficiency with physiologic replacement doses of corticosteroids are allowed
  • Prior treatment with a hypomethylating agent for treatment of AML or myelodysplastic syndrome (MDS)
  • Active malignancies (that is, progressing or requiring treatment in the last 24 months) other than the disease being treated under the study
  • Any active systemic infection
  • Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (that is, mannitol, an excipient of azacitidine)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com
Listed Location Countries  ICMJE Australia,   Brazil,   France,   Israel,   Italy,   Russian Federation,   Spain,   Switzerland,   Turkey
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT04023526
Other Study ID Numbers  ICMJE CR108609
2019-000473-23 ( EudraCT Number )
74494550AML2001 ( Other Identifier: Janssen Research & Development, LLC )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency
Responsible Party Janssen Research & Development, LLC
Study Sponsor  ICMJE Janssen Research & Development, LLC
Collaborators  ICMJE argenx BVBA
Investigators  ICMJE
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
PRS Account Janssen Research & Development, LLC
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP