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

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 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.


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

Arms:
- Experimental: Azacitidine 75 mg/m² and Cusatuzumab 10 mg/kg
- Experimental: Azacitidine 75 mg/m² and Cusatuzumab 20 mg/kg