Ficlatuzumab With High Dose Cytarabine in Relapsed and Refractory AML

Study Overview
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Brief Summary
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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.

Official Title
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Phase Ib Study of Ficlatuzumab With High Dose Cytarabine (HiDAC) in Relapsed and Refractory AML

Conditions
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Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Ficlatuzumab
* Drug: Cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Adequate renal function with creatinine ≤ 2.0 mg/dL The effects of ficlatuzumab on the developing human fetus are unknown. For this reason and because cytarabine is pregnancy category D, women of child-bearing potential and men must agree to use adequate contraception: hormone, barrier method of birth control, or abstinence prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and at least one month after completion of study drug administration. Ability to understand a written informed consent document, and the willingness to sign it Exclusion Criteria: 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 Chemotherapy, radiation, or immunotherapy, within 2 weeks prior to study entry, other than those specified in the inclusion criteria (hydroxyurea and hypomethylating agents) 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ficlatuzumab, Cytarabine<br>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<br>* 5-20 mg/kg; intravenous; Days 0, 14, 28, and 42. Number of cycles: until progression or unacceptable toxicity develops.<br>Drug: Cytarabine<br>* 2 g/m2; intravenous; Days 2-7; Number of cycles: until progression or unacceptable toxicity develops.<br>* Other names: HiDAC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Myeloid Leukemia, Ficlatuzumab, High Dose Cytarabine, antibody