Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06034470
Other study ID # RG1123378
Secondary ID NCI-2023-03572FH
Status Recruiting
Phase Phase 1
First received
Last updated
Start date December 18, 2023
Est. completion date December 31, 2027

Study information

Verified date January 2024
Source Fred Hutchinson Cancer Center
Contact Mary-Elizabeth Percival
Phone 206-606-1320
Email mperciva@uw.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase I trial finds the best dose of PVEK when given together with fludarabine, cytarabine, granulocyte colony-stimulating factor (G-CSF), and idarubicin, (FLAG-Ida) regimen and studies the effectiveness of this combination therapy in treating patients with newly diagnosed adverse risk acute myeloid leukemia (AML) and other high-grade myeloid neoplasms. PVEK is a monoclonal antibody linked to a chemotherapy drug. PVEK is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD123 receptors, and delivers the chemotherapy drug to kill them. Chemotherapy drugs, such as idarubicin, fludarabine, high-dose cytarabine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. G-CSF helps the bone marrow make more white blood cells in patients with low white blood cell count due to cancer treatment. Giving PVEK with the FLAG-Ida regimen may be a safe and effective treatment for patients with acute myeloid leukemia and other high-grade myeloid neoplasms.


Description:

OUTLINE: This is a dose-escalation study of PVEK. INDUCTION THERAPY: Patients receive PVEK intravenously (IV) on day 1 or day 1 and 22. Patients also receive G-CSF subcutaneously (SC) on days 0-5, fludarabine IV over 30 minutes on days 1-5, cytarabine IV over 2 hours on days 1-5, and idarubicin IV on days 1-3 in the absence of disease progression or unacceptable toxicity. Patients who still have cancer after the first cycle of study treatment may receive an additional cycle of intensive chemotherapy with PVEK. Patients who achieve a good response (remission) after the first 1 or 2 cycles of study continue to Post-Remission Therapy. POST-REMISSION THERAPY: Patients receive PVEK IV on day 1 of each cycle and high-dose cytarabine IV every 12 hours on days 1-6 of each cycle. Treatment repeats every 42 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration and may undergo bone marrow biopsy and blood sample collection throughout the trial. Patients also undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan during screening and as clinically indicated on trial. After completion of study treatment, patients are followed every 3 months for 5 years.


Recruitment information / eligibility

Status Recruiting
Enrollment 30
Est. completion date December 31, 2027
Est. primary completion date December 31, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age = 18 years - Diagnosis of untreated AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 5th edition of the World Health Organization (WHO) classification of hematolymphoid tumors. Patients with myelodysplastic, myeloproliferative, or myelodysplastic/myeloproliferative neoplasms and = 10% blasts in blood and/or bone marrow, are also eligible, as are patients with mixed phenotype acute leukemia (MPAL). Outside diagnostic material is acceptable to establish diagnosis; submission of peripheral blood specimen for flow cytometry performed at the study institution should be considered. Diagnostic material must have been submitted for cytogenetic and/or molecular testing as clinically appropriate - Cytogenetically/molecularly adverse-risk disease (European LeukemiaNet [ELN] 2022 criteria) - Expression of CD123 on immunophenotypically abnormal blasts, as assessed by local multiparameter flow cytometry. Evaluation of CD123 expression via immunohistochemistry is permissible, for example if flow cytometric assessment is not available - Medically fit, as defined by treatment-related mortality (TRM) score = 13.1 calculated with simplified model - The use of hydroxyurea prior to start of study therapy is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood cell count (WBC) > 100,000/µL or with concern for other complications of high tumor burden (e.g. disseminated intravascular coagulation) can be treated with leukapheresis prior to start of study therapy - Patients may have received low-intensity treatment (e.g. azacitidine/decitabine, lenalidomide, growth factors) for antecedent low-grade myeloid neoplasm (i.e. < 10% blasts in blood and bone marrow) - Bilirubin =< 1.5 x institutional upper limit of normal (IULN) unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x IULN unless elevation is thought to be due to hepatic infiltration by AML - Creatinine clearance >= 60 mL/min - Left ventricular ejection fraction >= 45%, assessed by multigated acquisition (MUGA) scan or echocardiography or other appropriate diagnostic modality and no clinical evidence of congestive heart failure - Fertile male and female subjects must be willing to use an effective contraceptive method before, during, and for at least 3 months after receiving the investigational agent - Provide written informed consent Exclusion Criteria: - Diagnosis of blast phase chronic myeloid leukemia (CML) - Patients with FLT3-mutated AML - Concomitant illness associated with a likely survival of < 1 year - Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with antimicrobials, and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired [e.g. known chronic viral hepatitis, human immunodeficiency virus (HIV)]). Patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24 hours. Patients with fever thought to be likely secondary to leukemia are eligible - Known hypersensitivity to any study drug or prior >= grade 3 hypersensitivity reactions to monoclonal antibodies - Confirmed or suspected pregnancy or active breast feeding - Treatment with any other investigational anti-leukemia agent

Study Design


Intervention

Procedure:
Biospecimen Collection
Undergo blood sample collection
Bone Marrow Aspiration
Undergo bone marrow aspirate
Bone Marrow Biopsy
Undergo bone marrow biopsy
Drug:
Cytarabine
Given IV
Procedure:
Echocardiography
Undergo ECHO
Drug:
Fludarabine
Given IV
Granulocyte Colony-Stimulating Factor
Given SC
Idarubicin
Given IV
Procedure:
Multigated Acquisition Scan
Undergo MUGA scan
Drug:
Pivekimab Sunirine
Given IV

Locations

Country Name City State
United States Fred Hutch/University of Washington Cancer Consortium Seattle Washington

Sponsors (2)

Lead Sponsor Collaborator
Fred Hutchinson Cancer Center ImmunoGen, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of dose-limiting toxicities during cycle 1 Dose-limiting toxicities (DLTs) for trial monitoring are defined as follows: a) Any Grade =4 organ toxicity; and b) prolonged severe myelosuppression, as defined by ANC <500/µL and platelet count <25,000/µL, for >42 days after initiation (day 1) of FLAG-Ida chemotherapy in the absence of residual disease (assessed by morphology and flow cytometrically/molecularly/cytogenetically). During cycle 1 (each cycle is 42 days)
Secondary Incidence of adverse events Will be assessed by the NCI CTCAE v.5. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data. Up to 5 years
Secondary Measurable residual disease (MRD) rates Will be estimated within the limits of the study with pivekimab sunirine (PVEK) + fludarabine, high-dose cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-Ida) across study cohorts. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data. Up to 5 years
Secondary MRD status MRD will be measured by multiparameter flow cytometry. All positive testing will be considered positive. Up to 5 years
Secondary Relapse-free survival Will be assessed within the limits of the study by the relationship between MRD status after induction therapy and relapse risk/time to relapse. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data. From the date of achievement of remission until the date of hematologic relapse or death from any cause, assessed up to 5 years
Secondary Overall survival Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data. From day 1 of study treatment to the date of death from any cause, up to 5 years
Secondary Complete remission rates Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data. Up to 5 years
Secondary Duration of cytopenias Will be evaluated by the impact of PVEK dosing regimens on the duration of cytopenias. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data. Up to 5 years
Secondary Proportion of patients receiving allogeneic hematopoietic cell transplantation Will be estimated within the limits of the study by the proportion of patients receiving allogeneic HCT in remission with PVEK + FLAG-Ida. Will be analyzed using standard methods for such data: Wilcoxon-rank sum tests for quantitative data; Fisher's exact test for categorical data; Kaplan-Meier, Cox regression, and log-rank tests for time-to-event data. Up to 5 years
See also
  Status Clinical Trial Phase
Recruiting NCT05400122 - Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer Phase 1
Recruiting NCT04460235 - Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma Phase 4
Completed NCT03678493 - A Study of FMT in Patients With AML Allo HSCT in Recipients Phase 2
Completed NCT04022785 - PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Phase 1
Recruiting NCT05424562 - A Study to Assess Change in Disease State in Adult Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy Receiving Oral Venetoclax Tablets in Canada
Terminated NCT03224819 - Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML) Early Phase 1
Completed NCT03197714 - Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia Phase 1
Active, not recruiting NCT04070768 - Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113 Phase 1
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Active, not recruiting NCT04107727 - Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML) Phase 2
Recruiting NCT04920500 - Bioequivalence of Daunorubicin Cytarabine Liposomes in Naive AML Patients N/A
Recruiting NCT04385290 - Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC) Phase 1/Phase 2
Recruiting NCT03897127 - Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics Phase 3
Active, not recruiting NCT04021368 - RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome Phase 1
Recruiting NCT03665480 - The Effect of G-CSF on MRD After Induction Therapy in Newly Diagnosed AML Phase 2/Phase 3
Completed NCT02485535 - Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant Phase 1
Enrolling by invitation NCT04093570 - A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers Phase 2
Recruiting NCT04069208 - IA14 Induction in Young Acute Myeloid Leukemia Phase 2
Recruiting NCT05744739 - Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML) Phase 1
Recruiting NCT04969601 - Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings Phase 1/Phase 2