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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04023526
Recruitment Status : Recruiting
First Posted : July 17, 2019
Last Update Posted : January 3, 2020
Sponsor:
Collaborator:
argenx BVBA
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: Azacitidine Drug: Cusatuzumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 29, 2019
Estimated Primary Completion Date : December 29, 2020
Estimated Study Completion Date : April 30, 2021


Arm Intervention/treatment
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.
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

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.
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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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).

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Minimum Serum Concentration (Cmin) of Cusatuzumab [ Time Frame: Up to 1.9 years ]
    Cmin is the minimum observed serum concentration.

  12. Maximum Serum Concentration (Cmax) of Cusatuzumab [ Time Frame: Up to 1.9 years ]
    Cmax is the maximum observed serum concentration.

  13. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04023526


Contacts
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Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
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Australia
St Vincents Hospital Sydney Recruiting
Darlinghurst, Australia, 2010
St Vincents Hospital Melbourne Recruiting
Fitzroy, Australia, 3065
The Alfred Hospital Recruiting
Melbourne, Australia, 3004
Royal Perth Hospital Recruiting
Perth, Australia, 6000
Westmead Hospital Recruiting
Westmead, Australia, 2145
Brazil
Hospital Estadual de Campinas - Centro de Hematologia e Hemoterapia Not yet recruiting
Campinas, Brazil, 13083-878
Hospital de Clínicas de Porto Alegre Not yet recruiting
Porto Alegre, Brazil, 90035-903
Hospital Nossa Senhora da Conceicao Not yet recruiting
Porto Alegre, Brazil, 91350-200
Instituto do Cancer do Estado de Sao Paulo 'Octavio Frias de Oliveira' - ICESP Not yet recruiting
Sao Paulo, Brazil, 01246-000
France
CHU d'Angers Recruiting
Angers, France, 49933
CHU Grenoble Recruiting
Grenoble cedex 9, France, 38043
Institut Paoli Calmettes Recruiting
Marseille Cedex 9, France, 13273
Centre Hospitalier Universitaire (CHU) de Bordeaux Hopital HautLeveque Centre Francois Magendie Recruiting
Pessac, France, 33600
CHU Lyon Sud Recruiting
Pierre - Bénite cedex, France, 69495
Institut Universitaire du Cancer Toulouse Oncopole Recruiting
Toulouse Cedex 9, France, 31059
CHRU Tours Hôpital Bretonneau Recruiting
Tours, France, 37000
Israel
Rambam Medical Center Recruiting
Haifa, Israel, 31096
Carmel Medical Center Not yet recruiting
Haifa, Israel, 3436212
Hadassah Medical Center Recruiting
Jerusalem, Israel, 9112001
Sheba Medical Center Not yet recruiting
Ramat Gan, Israel, 5262100
Tel Aviv Sourasky Medical Center Recruiting
Tel Aviv, Israel, 64239
Italy
Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna Not yet recruiting
Bologna, Italy, 40138
Azienda Ospedaliera Spedali Civili di Brescia Recruiting
Brescia, Italy, 25123
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Recruiting
Meldola, Italy, 47014
Istituto Europeo di Oncologia Recruiting
Milano, Italy, 20141
ASST Grande Ospedale Metropolitano Niguarda Not yet recruiting
Milano, Italy, 20162
Division of Hematology, Cardarelli Hospital Recruiting
Napoli, Italy, 80131
Azienda Sanitaria Universitaria Integrata di Udine Not yet recruiting
Udine, Italy, 33100
Russian Federation
Chelyabinck Regional Clinical Hospital Recruiting
Chelyabinsk, Russian Federation, 454076
Ekaterinburg City Clinical Hospital # 7 Recruiting
Ekaterinburg, Russian Federation, 620137
S.P. Botkin Moscow City Clinical Hospital Recruiting
Moscow, Russian Federation, 125284
City Clinical Hospital # 40 Recruiting
Moscow, Russian Federation, 129301
Nizhny Novgorod Regional Oncology Dispensary Recruiting
Nizhny Novgorod, Russian Federation, 603126
Ryazan Regional Clinical Hospital Recruiting
Ryazan, Russian Federation, 390039
City clinical hospital #15 Recruiting
Saint Petersburg, Russian Federation, 198205
Samara Region Clinical Hospital Recruiting
Samara, Russian Federation, 443095
Oncologic Dispensary No.2 Recruiting
Sochi, Russian Federation, 354057
St.-Petersburg Clinical Research Institute of Hematology and Transfusiology Recruiting
St. Petersburg, Russian Federation, 193024
Komi Republic Oncology dispensary Recruiting
Syktyvkar, Russian Federation, 167904
Spain
Hosp. de La Santa Creu I Sant Pau Recruiting
Barcelona, Spain, 08041
Inst. Cat. Doncologia-H Duran I Reynals Recruiting
Barcelona, Spain, 08908
Hosp. Univ. Vall D´Hebron Recruiting
Barcelona, Spain, 8035
Hosp. Reina Sofia Not yet recruiting
Cordoba, Spain, 14004
Hosp. Univ. Ramon Y Cajal Recruiting
Madrid, Spain, 28034
Hosp. Univ. 12 de Octubre Not yet recruiting
Madrid, Spain, 28041
Hosp. Univ. Son Espases Recruiting
Palma, Spain, 7120
Hosp. Quiron Madrid Pozuelo Recruiting
Pozuelo De Alarcon, Madrid, Spain, 28223
Hosp. Clinico Univ. de Salamanca Recruiting
Salamanca, Spain, 37007
Hosp. Univ. I Politecni La Fe Not yet recruiting
Valencia, Spain, 46026
Switzerland
Kantonsspital Aarau Recruiting
Aarau, Switzerland, 5001
INSELSPITAL, Universitätsspital Bern Recruiting
Bern, Switzerland, 3010
Hopitaux Universitaires de Geneve Recruiting
Geneve, Switzerland, 1205
UniversitaetsSpital Zuerich Not yet recruiting
Zürich, Switzerland
Turkey
Gulhane Egitim ve Arastirma Hastanesi Recruiting
Ankara, Turkey, 06010
Dr.Abdurrahman Yurtaslan Oncology Training and Research Hospital Recruiting
Ankara, Turkey, 06200
Ankara University Medical Faculty Hematology Department - Hematology Recruiting
Ankara, Turkey, 6100
Ondokuz Mayis Universitesi Tip Fakultesi Recruiting
Atakum, Turkey, 55139
Istanbul Egitim ve Arastirma Hastanesi Recruiting
Istanbul, Turkey, 34098
Dokuz Eylul Universitesi Tip Fakultesi Recruiting
İzmir, Turkey, 35210
Karadeniz Teknik University Medical Faculty Recruiting
Trabzon, Turkey, 61080
Sponsors and Collaborators
Janssen Research & Development, LLC
argenx BVBA
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Additional Information:
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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04023526    
Other Study ID Numbers: CR108609
2019-000473-23 ( EudraCT Number )
74494550AML2001 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: July 17, 2019    Key Record Dates
Last Update Posted: January 3, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
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

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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
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors