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

M.D. Anderson Cancer Center

Status and phase: Completed; Phase 2

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

Treatments: Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT01664897

P30CA016672 (U.S. NIH Grant/Contract)

2012-0060 (Other Identifier)

NCI-2012-02073 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Treatment (erlotinib hydrochloride)

Experimental group

Description:

Patients receive erlotinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Other: Laboratory Biomarker Analysis

Drug: Erlotinib Hydrochloride