Clinical trial NCT01664897: Erlotinib Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official title: A Pilot Phase II Study of Erlotinib for the Treatment of Patients With Refractory/Relapsed AML
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: Astellas Pharma Inc
First posted: 2012-08-14
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Participants With a Response
timeFrame: Up to 3 months post-treatment
measure: Incidence of Clinically Significant, Non-hematologic Grade 3 or 4 Toxicities at Least Possibly Related to Erlotinib Hydrochloride
timeFrame: Up to 30 days
measure: Overall Survival
timeFrame: Up to 97 weeks
measure: Event-free Survival
timeFrame: Up to 21 weeks
Secondary outcomes:
measure: Biomarker Expressions
timeFrame: Up to 30 days
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jorge Cortes
role: PRINCIPAL_INVESTIGATOR
References: