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)
Overview
- Phase
- Phase 2
- Intervention
- Ficlatuzumab
- Conditions
- Acute Myeloid Leukemia
- Sponsor
- AVEO Pharmaceuticals, Inc.
- Primary Endpoint
- Overall Response Rate (ORR)
- Status
- Withdrawn
- Last Updated
- 6 years ago
Overview
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.
Investigators
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
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
Arms & Interventions
Ficlatuzumab with HiDAC
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.
Intervention: Ficlatuzumab
Ficlatuzumab with HiDAC
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.
Intervention: Cytarabine
HiDAC alone
Cytarabine 2 g/m2 IV per day on Days 1 through 6
Intervention: Cytarabine
Outcomes
Primary Outcomes
Overall Response Rate (ORR)
Time Frame: Approximately 13 months (through study treatment completion)
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 Outcomes
- 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)