A Phase 1 Study of Cusatuzumab Plus Azacitidine in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Who Are Not Candidates for Intensive Treatment
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- OncoVerity, Inc.
- Enrollment
- 6
- Locations
- 5
- Primary Endpoint
- Part 1 and Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Study Overview
Brief Summary
The purpose of this study is to determine the recommended Phase 2 dose and evaluate safety profile of cusatuzumab in combination with azacitidine in Japanese participants with treatment naïve acute myeloid leukemia (AML) who are not candidates for intensive treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •For acute myeloid leukemia (AML) participants: AML according to World Health Organization (WHO) 2016 criteria and fulfilling all of the following criteria:(a) more than or equal to (>=) 75 years of age, or younger participants who are not eligible for or not willing to receive an intensive treatment (including stem cell transplantation) with curative intent and (b) previously untreated AML (except: emergency leukapheresis, 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 cusatuzumab [Part 1] or azacitidine [Part 2]). All trans retinoic acid (ATRA) treatment for presumed acute promyelocytic leukemia (APL) is permitted but must be discontinued at least 1 day prior to the start of cusatuzumab (Part 1) or azacitidine (Part 2)
- •For Myelodysplastic Syndrome (MDS) participants (only for Part 2): MDS according to WHO 2016 criteria and fulfilling all of the following criteria: (a) Not eligible for or not willing to receive allogenic stem cell transplantation,(b) very high or high-risk MDS according to Revised International Prognostic Scoring System (IPSS-R) and (c) previously untreated MDS (except: transfusion and/or cytokine therapy including erythropoietin)
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
- •Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study
- •A woman of childbearing potential must have a negative highly sensitive serum (beta human chorionic gonadotropin [beta hCG]) or urine pregnancy at screening
Exclusion Criteria
- •Acute promyelocytic leukemia (APL) with t (15;17), or its molecular equivalent promyelocytic leukemia retinoic acid receptor (PML RAR alpha)
- •Leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system
- •Known allergies, hypersensitivity, or intolerance to cusatuzumab or azacitidine or its excipients (example, mannitol, an excipient of azacitidine)
- •Prior treatment with a hypomethylating agent for treatment of AML or MDS
- •A diagnosis of other malignancy that requires concurrent nonsurgical treatment
Arms & Interventions
Part 1 (Dose Finding): Cusatuzumab + Azacitidine
Participants with acute myeloid leukemia (AML) will receive cusatuzumab intravenously (IV) in combination with azacitidine subcutaneously (SC) or IV. The dose levels will be escalated based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
Intervention: Cusatuzumab (Drug)
Part 1 (Dose Finding): Cusatuzumab + Azacitidine
Participants with acute myeloid leukemia (AML) will receive cusatuzumab intravenously (IV) in combination with azacitidine subcutaneously (SC) or IV. The dose levels will be escalated based on the decisions of the Study Evaluation Team (SET) until the recommended Phase 2 Dose (RP2D) has been identified.
Intervention: Azacitidine (Drug)
Part 2 (Dose Expansion): Cusatuzumab + Azacitidine
Participants with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) will receive cusatuzumab intravenously (IV) at the recommended Phase 2 dose (RP2D) determined in Part 1 in combination with azacitidine subcutaneously (SC) or IV.
Intervention: Cusatuzumab (Drug)
Part 2 (Dose Expansion): Cusatuzumab + Azacitidine
Participants with acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) will receive cusatuzumab intravenously (IV) at the recommended Phase 2 dose (RP2D) determined in Part 1 in combination with azacitidine subcutaneously (SC) or IV.
Intervention: Azacitidine (Drug)
Outcomes
Primary Outcomes
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 3 years
Number of participants with AEs and SAEs will be reported.
Part 1 and Part 2: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Time Frame: Up to 42 days
Severity of DLT as assessed by NCI-CTCAE in participants will be reported.
Part 1 and Part 2: Number of Participants with Dose-Limiting Toxicity (DLTs)
Time Frame: Up to 42 days
Number of participants with DLTs will be reported.
Secondary Outcomes
- Part 1 and Part 2: Overall Survival (OS)(Up to 3 years)
- Part 1 and Part 2: Time to Response(Up to 3 years)
- Part 1 and Part 2: Duration of Response(Up to 3 years)
- Part 1 and Part 2: Maximum Serum Concentration (Cmax) of Cusatuzumab(Up to 3 years)
- Part 1 and Part 2: Serum Trough Concentration (Ctrough) of Cusatuzumab(Up to 3 years)
- Part 1 and Part 2: Percentage of Participants with Complete Response (CR)(Up to 9 months)
- Part 1: Objective Response Rate (ORR)(Up to 6 months)
- Part 2: Objective Response Rate (ORR)(Up to 9 months)
- Part 1 and Part 2: Red Blood Cell (RBC) or Platelets Transfusion Independence(Up to 3 years)
- Part 2: Percentage of Participants with Hematologic Improvement (HI)(Up to 9 months)