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.
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 (ADCC) 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. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
103
Azacitidine SC or IV will be administered at a standard dose of 75 mg/m\^2 on days 1-7 of each cycle.
Cusatuzumab IV will be administered as 10 mg/kg or 20 mg/kg on days 3 and 17 of each cycle.
Percentage of Participants With Complete Remission (CR)
Complete remission based on European Leukemia Network (ELN) 2017 response criteria. Defined as bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absences of extramedullary disease; ANC \>= 1.0 x10\^9/L; platelet count \>=100 x 10\^9/L
Time frame: Up to 3 years and 5 months
Percentage of Participants With CR With Partial Hematological Recovery (CRh)
CRh defined as meeting all criteria for CR except ANC \>0.5x10\^9/L and platelet count \>50x10\^9/L
Time frame: Up to 3 years and 5 months
Percentage of Participants With CR Plus CRh
CR plus CRh based on ELN 2017 response criteria. CR defined as bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absences of extramedullary disease; ANC \>= 1.0 x10\^9/L; platelet count \>=100 x 10\^9/L CRh defined as meeting all criteria for CR except ANC \>0.5x10\^9/L and platelet count \>50x10\^9/L
Time frame: Up to 3 years and 5 months
Percentage of Participants With CR With Incomplete Recovery (CRi)
CRi based on ELN 2017 response criteria. Defined as meeting all CR criteria except for residual neutropenia (ANC \<1.0x10\^9/L) or thrombocytopenia (platelets \<100x10\^9/L)
Time frame: Up to 3 years and 5 months
Overall Response Rate (ORR)
ORR is defined as percentage of participants with CR, CRh and CRi based on ELN 2017 response criteria.
Time frame: Up to 3 years and 5 months
Percentage of Participants With CR Without MRD
CR without minimal residual disease (MRD) defined as less than 1 blast or leukemic stem cell in 1,000 leukocytes (MRD level \<10\^-3 by flow cytometry).
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St Vincents Hospital Sydney
Darlinghurst, Australia
St Vincents Hospital Melbourne
Fitzroy, Australia
The Alfred Hospital
Melbourne, Australia
Royal Perth Hospital
Perth, Australia
Westmead Hospital
Westmead, Australia
Universidade Estadual De Campinas
Campinas, Brazil
Hospital das Clinicas de Porto Alegre
Porto Alegre, Brazil
CHU d'Angers
Angers, France
CHU Grenoble
Grenoble, France
Institut Paoli Calmettes
Marseille, France
...and 46 more locations
Time frame: Up to 3 years and 5 months
Percentage of Participants With Negative MRD Who Achieved CR, CRh, CRi, or Morphologic Leukemia-free State (MLFS)
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 frame: Up to 3 years and 5 months
Time to First Response
Defined as time from randomization to achieving the first response of CR, CRh, or CRi.
Time frame: Up to 3 years and 5 months
Duration of First Response
Defined as time from achieving the first response of CR, CRh, or CRi to disease relapse or death from any cause.
Time frame: Up to 3 years and 5 months
Red Blood Cell (RBC) and/or Platelets Transfusion Independence
Defined as a period of at least 56 consecutive days with no transfusion of RBC and/or platelets between first dose of study drug and the last dose of study drug +30 days.
Time frame: Up to 3 years and 5 months
Cusatuzumab Minimum Serum Concentration (Cmin)
Cmin is the minimum cusatuzumab serum concentration observed at Cycle 1 Day 3
Time frame: Cycle 1 Day 3
Maximum Serum Concentration (Cmax) of Cusatuzumab
Cmax is the maximum cusatuzumab serum concentration observed at Cycle 1 Day 3.
Time frame: Cycle 1 Day 3
Number of Participants With Anti-cusatuzumab Antibodies
Number of participants exhibiting anti-drug antibodies for cusatuzumab.
Time frame: Up to 3 years and 5 months