Ficlatuzumab With High Dose Cytarabine in Relapsed and Refractory AML

NCT02109627 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 139510NCI-2015-00749
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if ficlatuzumab when combined with cytarabine, a standard treatment for AML, is safe to give to patients and to determine the best dose to give. The study doctors want to see what effects, good and/or bad, the study drug has on subjects and their AML. The study will look at what side effects subjects may have and how subjects feel after receiving the study drug.

Conditions

Acute Myeloid Leukemia; Relapsed Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Ficlatuzumab; High Dose Cytarabine; antibody

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT) for ficlatuzumab when administered with HiDAC

  Up to 2 years

• Maximum Tolerated Dose (MTD) for ficlatuzumab when administered with HiDAC

  Up to 2 years

Secondary Outcomes (3)

• Preliminary activity of ficlatuzumab in combination with HiDAC in patients with relapsed or refractory AML

  Up to 2 years

• Functional status for patients receiving ficlatuzumab and HiDAC

  Up to 2 years

• Quality of life for patients receiving ficlatuzumab and HiDAC

  Up to 2 years

Other Outcomes (2)

• Overall survival of patients receiving ficlatuzumab in combination with HiDAC

  Up to 2 years

• Candidate biomarkers for response to combination therapy

  Up to 2 years

Study Arms (1)

Ficlatuzumab, Cytarabine

EXPERIMENTAL

Ficlatuzumab 5-20 mg/kg; intravenous; Days 0, 14, 28, 42; Number of cycles: until progression or unacceptable toxicity develops. Cytarabine 2 g/m2; intravenous; Days 2-7; Number of cycles: until progression or unacceptable toxicity develops.

Drug: Ficlatuzumab; Drug: Cytarabine

Interventions

Ficlatuzumab DRUG

5-20 mg/kg; intravenous; Days 0, 14, 28, and 42. Number of cycles: until progression or unacceptable toxicity develops.

Ficlatuzumab, Cytarabine

Cytarabine DRUG

2 g/m2; intravenous; Days 2-7; Number of cycles: until progression or unacceptable toxicity develops.

Also known as: HiDAC

Ficlatuzumab, Cytarabine

Eligibility Criteria

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

You may qualify if:

• Relapsed or refractory AML as defined by one of the following criteria:
• First relapse within 12 months after date of first Complete Response (CR) or complete repsonse with incomplete hematologic recovery (CRi)
• Persistent AML documented by bone marrow biopsy at least 28 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 first induction cycle day 1
• Age \>=18
• Prior induction therapy had to include no more than two cycles of cytotoxic chemotherapy and at least one induction cycle must have consisted of an anthracycline or anthracenedione and cytarabine combination with a reasonable schedule/dose according to the discretion of the investigator
• Histologically confirmed AML by hematopathology review performed within four weeks prior to study entry
• Ejection fraction \>=40% by transthoracic echocardiogram or radionuclide ventriculogram, i.e. multigated acquisition (MUGA) scan
• Treatment for non-hematologic malignancy greater than 6 months prior to enrollment is acceptable.
• Transplantation for AML (allogeneic or autologous) allowed unless within 90 days of study entry
• No active graft versus host disease (GVHD) or immunosuppression for prevention or treatment of GVHD within two weeks of study entry
• Prior treatment of myelodysplastic syndrome or myeloproliferative neoplasm with hypomethylating agent acceptable.
• Cytoreduction therapy with plasmapheresis or hydroxyurea acceptable.
• Females must have a negative serum pregnancy test 24 hours prior to the start of treatment or be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months)
• Adequate liver function as defined by total bilirubin ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with known Gilbert's syndrome) and aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 3 times upper limit of normal, unless these are thought to be due to AML

You may not qualify if:

• Acute promyelocytic leukemia (FAB M3 AML)
• More than 2 cycles of prior induction therapy for AML
• Allogeneic or autologous transplant for AML with infusion of stem cells within 90 days of study entry or on active immunosuppressive therapy for graft versus host disease (GVHD) within 2 weeks before study entry
• Cytarabine containing regimen in excess of 2 g/m2/day within 6 months of study entry
• Known active HIV, hepatitis B or C or infection. Exception for patients with hepatitis B on antivirals and low viral load, to be determined at the discretion of the investigator.
• Uncontrolled infection
• Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
• Active second malignancy that in the opinion of the PI may interfere with or be adversely affected by this treatment.
• Prior exposure to the investigational agent or anti-c-Met, anti-HGF or anti-VEGF directed therapy within six months prior to study entry
• Prior grade 4 toxicity attributed to cytarabine
• Known or suspected drug sensitivity to cytarabine or the investigational agent ficlatuzumab
• Inability to provide consent
• Pregnant women are excluded from this study because the effect of ficlatuzumab on the developing fetus remains unknown and that cytarabine is a pregnancy risk category D drug with known teratogenic or abortifacient effects. Because of the potential adverse events in nursing infants secondary to treatment of the mother with ficlatuzumab and cytarabine, breastfeeding should be discontinued while on study. Patients who become pregnant while on study will be removed from the study once the pregnancy is confirmed.

Sponsors & Collaborators

• C. Babis Andreadis: lead
• AVEO Pharmaceuticals, Inc.: collaborator
• Gateway for Cancer Research: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

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 Officials

• Charalambos Andreadis, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Clinical Medicine

Study Record Dates

• First Submitted: January 23, 2014
• First Posted: April 10, 2014
• Study Start: May 1, 2015
• Primary Completion: December 2, 2019
• Study Completion: December 2, 2019
• Last Updated: March 24, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)