A Study of Ficlatuzumab With HiDAC and HiDAC Alone in Adults With Relapsed or Refractory Acute Myeloid Leukemia

NCT04100330 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: AV-299-19-207
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase 2, randomized, open-label, multicenter study to evaluate the safety and efficacy of ficlatuzumab in combination with high-dose cytarabine (HiDAC) and HiDAC alone in subjects with relapsed or refractory acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  To estimate the overall response rate (ORR) (complete remission \[CR\] + CR with incomplete hematologic recovery \[CRi\]) of ficlatuzumab in combination with high-dose cytarabine (HiDAC) and HiDAC alone in adults with relapsed or refractory acute myeloid leukemia (AML)

  Approximately 13 months (through study treatment completion)

Secondary Outcomes (3)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  Approximately 14 months (through 30 days after the last subject completes treatment)

• Overall Survival (OS)

  For up to one year after the end of study treatment

• Disease-Free Survival (DFS)

  For up to one year after the end of study treatment

Study Arms (2)

Ficlatuzumab with HiDAC

EXPERIMENTAL

Ficlatuzumab 20 mg/kg intravenously (IV) on Days 1 and 15 in combination with cytarabine 2 g/m2 IV per day on Days 2 through 7. Up to two additional doses can be administered - on Day 29, or on Days 29 and 43, if prolonged myelosuppression is experienced.

Biological: Ficlatuzumab; Drug: Cytarabine

HiDAC alone

ACTIVE COMPARATOR

Cytarabine 2 g/m2 IV per day on Days 1 through 6

Drug: Cytarabine

Interventions

Ficlatuzumab BIOLOGICAL

Ficlatuzumab is a selective recombinant humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G subclass 1 monoclonal antibody which blocks the MET tyrosine kinase receptor.

Also known as: AV-299

Ficlatuzumab with HiDAC

Cytarabine DRUG

Cytarabine is a chemotherapy agent. Chemotherapy agents are medications that kill cancer cells.

Also known as: Ara-C, Arabinosylcytosine

Ficlatuzumab with HiDAC; HiDAC alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of AML according to the WHO criteria, which defines relapsed or refractory to induction therapy as follows:
• First relapse within 12 months after date of first CR or CRi
• Persistent AML documented by bone marrow biopsy at least 29 days after Day 1 of the first induction cycle of cytotoxic chemotherapy
• Hypercellular bone marrow with greater than 20% cellularity and 10% blasts at least 14 days after the first induction cycle Day 1
• Age ≥18 years
• Prior induction therapy, consisting of no more than 2 cycles of cytotoxic chemotherapy with at least one of the cycles consisting of anthracycline and cytarabine with reasonable schedule/dose intensity according to the discretion of the Investigator
• Ejection fraction ≥40% by echocardiogram or multigated acquisition (MUGA) scan
• Cytoreduction therapy with leukapheresis or hydroxyurea is allowed
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Clinical laboratory values meeting the following criteria before Day 1 (Cycle 1, Day 1):
• An estimated glomerular filtration rate of ≥ 60mL/min based on Cockcroft-Gault equation calculated using serum creatinine levels
• Total bilirubin ≤2.0 mg/dL (≤3.0 mg/dL for subjects with known Gilbert's syndrome)
• Aspartate aminotransferase (AST) or ALT ≤2.5 × ULN, unless thought to be due to AML
• Activated partial thromboplastin time ≤1.5 × ULN and prothrombin time/international normalized ratio (PT/INR) ≤1.5 × ULN if not on anticoagulation therapy. Subjects receiving anticoagulation therapy with an agent such as warfarin or low-molecular weight heparin may be allowed to participate with the therapeutic range established before initiation of study treatment.
• For female subjects of childbearing potential, documentation of negative serum pregnancy test before randomization

You may not qualify if:

• History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational agent or cytarabine
• Acute promyelocytic leukemia (AML French-American-British classification M3)
• More than 2 cycles of prior induction therapy for AML
• Prior treatment with intermediate- or HiDAC (≥1 gm/m2)
• Allogeneic or autologous hematopoietic cell transplantation within 90 days of study entry
• Prior treatment with any other investigational drugs, biologics, or devices, within 4 weeks before Day 1
• Active graft versus host disease or immunosuppression for prevention or treatment of graft versus host disease within 4 weeks of study entry
• Chemotherapy or radiation therapy within 1 week before study entry, other than hypomethylating agents or hydroxyurea used for cytoreduction
• Significant cardiovascular disease, including:
• Cardiac failure New York Heart Association class III or IV
• Myocardial infarction, severe or unstable angina within 6 months before Day 1
• History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation)
• Any other medical condition or psychiatric condition that, in the opinion of the Investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results
• History of prior/concurrent malignancy whose natural history or ongoing treatment is expected to interfere with the safety or efficacy assessment of the intervention
• Known seropositive or active HIV

Sponsors & Collaborators

• AVEO Pharmaceuticals, Inc.: lead
• Biodesix, Inc.: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

ficlatuzumab; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: September 24, 2019
• Study Start: January 31, 2020
• Primary Completion: March 27, 2020
• Study Completion: March 27, 2020
• Last Updated: March 31, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share