A Study of Ficlatuzumab With HiDAC and HiDAC Alone in Adults With Relapsed or Refractory Acute Myeloid Leukemia (CyFi2)
Primary Purpose
Acute Myeloid Leukemia
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Ficlatuzumab
Cytarabine
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
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
- Histologically confirmed AML by hematopathology review performed within 4 weeks of study entry. Secondary AML due to progression of myelodysplastic syndrome or myeloproliferative neoplasms is acceptable for inclusion.
- Prior treatment for myelodysplastic syndrome or myeloproliferative neoplasm with hypomethylating agent or targeted agent is acceptable for inclusion
- 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
- For female subjects of childbearing potential and male subjects whose sexual partners are of childbearing potential, agreement to use an effective method of contraception during the study and for at least 90 days after the last dose of ficlatuzumab. Effective birth control includes (a) intrauterine device plus 1 barrier method; (b) oral, implantable, or injectable contraceptive plus 1 barrier method; or (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
- Ability to give written informed consent and comply with protocol requirements
Exclusion Criteria:
- 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)
- Significant thrombotic or embolic events within 3 months before Day 1 (significant thrombotic or embolic events include, but are not limited to, venous thromboembolism, stroke, or transient ischemic attack). Catheter-related thrombosis is not a cause for exclusion. Diagnosis of deep vein thrombosis or pulmonary embolism is allowed if it occurred >3 months before Day 1 and anticoagulation therapy is completed before Day 1.
- 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
- Active hepatitis B or C infection
- Uncontrolled systemic fungal, bacterial, or viral infections
- For female subjects, pregnant or breastfeeding
- Prior exposure to the investigational agent or anti-c-MET, or anti-HGF within 6 months before study entry
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ficlatuzumab with HiDAC
HiDAC alone
Arm Description
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.
Cytarabine 2 g/m2 IV per day on Days 1 through 6
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
To evaluate the safety and tolerability of ficlatuzumab when administered with HiDAC and HiDAC alone
Overall Survival (OS)
To estimate the overall survival (OS) rate of ficlatuzumab in combination with HiDAC and HiDAC alone in adults with relapsed or refractory AML
Disease-Free Survival (DFS)
To estimate the disease-free survival (DFS) rate of ficlatuzumab in combination with HiDAC and HiDAC alone in subjects achieving CR
Full Information
NCT ID
NCT04100330
First Posted
September 12, 2019
Last Updated
March 27, 2020
Sponsor
AVEO Pharmaceuticals, Inc.
Collaborators
Biodesix, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04100330
Brief Title
A Study of Ficlatuzumab With HiDAC and HiDAC Alone in Adults With Relapsed or Refractory Acute Myeloid Leukemia
Acronym
CyFi2
Official Title
A Phase 2, Randomized, Open-Label, Multicenter Study of Ficlatuzumab in Combination With High-Dose Cytarabine (HiDAC) and HiDAC Alone in Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Withdrawn
Why Stopped
Urgent shift among clinical sites toward efforts to combat COVID-19 pandemic;impacted feasibility of completing study within shelf-life of current IP supply
Study Start Date
January 31, 2020 (Anticipated)
Primary Completion Date
March 27, 2020 (Actual)
Study Completion Date
March 27, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AVEO Pharmaceuticals, Inc.
Collaborators
Biodesix, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ficlatuzumab with HiDAC
Arm Type
Experimental
Arm Description
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.
Arm Title
HiDAC alone
Arm Type
Active Comparator
Arm Description
Cytarabine 2 g/m2 IV per day on Days 1 through 6
Intervention Type
Biological
Intervention Name(s)
Ficlatuzumab
Other Intervention Name(s)
AV-299
Intervention Description
Ficlatuzumab is a selective recombinant humanized hepatocyte growth factor (HGF) inhibitory immunoglobulin G subclass 1 monoclonal antibody which blocks the MET tyrosine kinase receptor.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Ara-C, Arabinosylcytosine
Intervention Description
Cytarabine is a chemotherapy agent. Chemotherapy agents are medications that kill cancer cells.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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)
Time Frame
Approximately 13 months (through study treatment completion)
Secondary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
To evaluate the safety and tolerability of ficlatuzumab when administered with HiDAC and HiDAC alone
Time Frame
Approximately 14 months (through 30 days after the last subject completes treatment)
Title
Overall Survival (OS)
Description
To estimate the overall survival (OS) rate of ficlatuzumab in combination with HiDAC and HiDAC alone in adults with relapsed or refractory AML
Time Frame
For up to one year after the end of study treatment
Title
Disease-Free Survival (DFS)
Description
To estimate the disease-free survival (DFS) rate of ficlatuzumab in combination with HiDAC and HiDAC alone in subjects achieving CR
Time Frame
For up to one year after the end of study treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Histologically confirmed AML by hematopathology review performed within 4 weeks of study entry. Secondary AML due to progression of myelodysplastic syndrome or myeloproliferative neoplasms is acceptable for inclusion.
Prior treatment for myelodysplastic syndrome or myeloproliferative neoplasm with hypomethylating agent or targeted agent is acceptable for inclusion
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
For female subjects of childbearing potential and male subjects whose sexual partners are of childbearing potential, agreement to use an effective method of contraception during the study and for at least 90 days after the last dose of ficlatuzumab. Effective birth control includes (a) intrauterine device plus 1 barrier method; (b) oral, implantable, or injectable contraceptive plus 1 barrier method; or (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
Ability to give written informed consent and comply with protocol requirements
Exclusion Criteria:
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)
Significant thrombotic or embolic events within 3 months before Day 1 (significant thrombotic or embolic events include, but are not limited to, venous thromboembolism, stroke, or transient ischemic attack). Catheter-related thrombosis is not a cause for exclusion. Diagnosis of deep vein thrombosis or pulmonary embolism is allowed if it occurred >3 months before Day 1 and anticoagulation therapy is completed before Day 1.
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
Active hepatitis B or C infection
Uncontrolled systemic fungal, bacterial, or viral infections
For female subjects, pregnant or breastfeeding
Prior exposure to the investigational agent or anti-c-MET, or anti-HGF within 6 months before study entry
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of Ficlatuzumab With HiDAC and HiDAC Alone in Adults With Relapsed or Refractory Acute Myeloid Leukemia
We'll reach out to this number within 24 hrs