Erlotinib Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This pilot phase II trial studies how well erlotinib hydrochloride works in treating patients with relapsed or refractory acute myeloid leukemia. Erlotinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the efficacy of erlotinib (erlotinib hydrochloride) in patients with refractory or relapsed acute myeloid leukemia (AML). II. To determine the safety and tolerability of erlotinib in this patient population. SECONDARY OBJECTIVES: I. To investigate inhibitory effect of this drug on spleen tyrosine kinase (SYK) and its down-stream targets such as mitogen-activated protein kinase 8 (JNK), mitogen-activated protein kinase (MAPK) and mitogen-activated protein kinase 1 (Erk). II. To evaluate its role in janus kinase (Jak)/signal transducer and activator of transcription (STAT) pathway and to investigate erlotinib-mediated cell death and/or differentiation. III. To quantitate concentrations of plasma erlotinib. OUTLINE: Patients receive erlotinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

Official Title
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A Pilot Phase II Study of Erlotinib for the Treatment of Patients With Refractory/Relapsed AML

Conditions
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Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome, Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11, Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11, Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1, Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A, Adult Acute Promyelocytic Leukemia With PML-RARA, Alkylating Agent-Related Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Previously Treated Myelodysplastic Syndrome, Recurrent Adult Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: Erlotinib Hydrochloride
* Other: Laboratory Biomarker Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with AML who have either been refractory to prior therapy or have relapsed after prior therapy; patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) who received therapy with a hypomethylating agent and progress to AML are eligible if they have received any therapy for MDS and failed (i.e., lack or loss of response) regardless of whether they have received therapy for AML or not; the World Health Organization (WHO) classification will be used for AML Eastern Cooperative Oncology Group (ECOG) performance status =< 2 Total bilirubin =< 2 x upper limit of normal (ULN) Alanine aminotransferase (ALT) =< 2.5 x ULN Creatinine =< 2 x ULN Patients must provide written informed consent Patients must have been off chemotherapy for 2 weeks prior to entering this study, unless there is evidence of rapidly progressive disease, and must have recovered from the clinically significant toxic effects of that therapy to at least grade 1; use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy Patients-both males and females-with reproductive potential (i.e., menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study; women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to initiation of study Exclusion Criteria: Patients with known allergy or hypersensitivity to erlotinib Patients with any other known disease (except carcinoma in-situ) concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes; cardiovascular disease including congestive heart failure New York Heart Association [NYHA] class III or IV, myocardial infarction within 6 months, and poorly controlled hypertension; chronic renal failure; or active uncontrolled infection) which, in the opinion of the investigator could compromise participation in the study Patients unwilling or unable to comply with the protocol Significant gastrointestinal disorders that may interfere with absorption of erlotinib Patients who can receive a stem cell transplant within 4 weeks

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: Treatment (erlotinib hydrochloride)<br>Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: Erlotinib Hydrochloride<br>* Given PO<br>* Other names: Tarceva;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With a Response | Overall Response is complete remission (CR) + CR with incomplete hematologic recovery (CRi) + Partial remission (PR) + Hematologic improvement (HI) + Morphologic Leukemia-Free State (MLF). (CR) is Bone marrow; </=5% blasts, no Auer rods or extramedullary disease and peripheral blood counts >/= 1.0x10^9/L Neutrophils, >/= 100x10^9/L platelets and no circulating blasts. (CRi), same as CR for bone marrow and <1.0x10^9/L neutrophils and < 100x10^9/L platelets in peripheral blood counts. PR is all CR criteria if abnormal prior to treatment except >/= 50%reduction in bone marrow blast but still > 5%. MLF is </=5% myeloblasts on bone marrow . HI response must be described by the number of positively affected cell lines.. | Up to 3 months post-treatment | 
| Incidence of Clinically Significant, Non-hematologic Grade 3 or 4 Toxicities at Least Possibly Related to Erlotinib Hydrochloride | Safety summaries will include tabulations in the form of tables and listings. The number of participants affected by treatment-emergent adverse events will be reported. | Up to 30 days | 
| Overall Survival | Time from date of treatment start until date of death due to any cause or last Follow-up. | Up to 97 weeks | 
| Event-free Survival | Time from date of treatment start until the date of first objective documentation of disease-relapse. | Up to 21 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker Expressions | Descriptive statistics will be used to summarize the expression of biomarkers and the concentrations of plasma erlotinib hydrochloride. The Wilcoxon rank sum test will be used to compare the expressions of biomarkers and concentrations of plasma erlotinib hydrochloride between patients with and without response. | Up to 30 days |