Status:

WITHDRAWN

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

Lead Sponsor:

AVEO Pharmaceuticals, Inc.

Collaborating Sponsors:

Biodesix, Inc.

Conditions:

Acute Myeloid Leukemia

Eligibility:

All Genders

18+ years

Phase:

PHASE2

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 relap...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

January 31 2020

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

March 27 2020

Estimated Enrollment :

Patients enrolled

Trial Details

Trial ID

NCT04100330

Start Date

January 31 2020

End Date

March 27 2020

Last Update

March 31 2020

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