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

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01664897
• Collaborator: National Cancer Institute (NCI) (NIH), Astellas Pharma Inc (Industry)
• Enrollment: 29
• Location: 1
• Arm: 1
• Actual Duration (Months): 65.3
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the efficacy of erlotinib (erlotinib hydrochloride) in patients with refractory or relapsed acute myeloid leukemia (AML).

2. To determine the safety and tolerability of erlotinib in this patient population.

SECONDARY OBJECTIVES:

1. 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).

2. 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.

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pilot Phase II Study of Erlotinib for the Treatment of Patients With Refractory/Relapsed AML
• Actual Study Start Date: May 16, 2013
• Actual Primary Completion Date: Oct 25, 2018
• Actual Study Completion Date: Oct 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (erlotinib hydrochloride) 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; Given PO; Other Names: Cp-358,774 OSI-774 Tarceva ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Participants With a Response [Up to 3 months post-treatment]

   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..

2. Incidence of Clinically Significant, Non-hematologic Grade 3 or 4 Toxicities at Least Possibly Related to Erlotinib Hydrochloride [Up to 30 days]

   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.

3. Overall Survival [Up to 97 weeks]

   Time from date of treatment start until date of death due to any cause or last Follow-up.

4. Event-free Survival [Up to 21 weeks]

   Time from date of treatment start until the date of first objective documentation of disease-relapse.

Secondary Outcome Measures

1. Biomarker Expressions [Up to 30 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)
• Astellas Pharma Inc

Investigators

• Principal Investigator: Jorge Cortes, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 19, 2013

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01664897
• Other Study ID Numbers: 2012-0060; NCI-2012-02073; 2012-0060; P30CA016672
• First Posted: Aug 14, 2012
• Last Update Posted: Jan 7, 2020
• Last Verified: Dec 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Leukemia, Promyelocytic, Acute; Myelodysplastic Syndromes; Syndrome; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	Recruitment Period: May 2013 to May 2014

Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/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. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	29
COMPLETED	29
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/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. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
Overall Participants	29
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	13 44.8%
>=65 years	16 55.2%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	12 41.4%
Male	17 58.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 10.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 17.2%
White	20 69%
More than one race	0 0%
Unknown or Not Reported	1 3.4%
Region of Enrollment (Count of Participants)
United States	29 100%

Outcome Measures

1. Primary Outcome

Title	Participants With a Response
Description	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..
Time Frame	Up to 3 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/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. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	29
Count of Participants [Participants]	3 10.3%

2. Primary Outcome

Title	Incidence of Clinically Significant, Non-hematologic Grade 3 or 4 Toxicities at Least Possibly Related to Erlotinib Hydrochloride
Description	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.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/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. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	29
Fatigue	10 34.5%
Diarrhea	10 34.5%
Nausea	8 27.6%
Rash	7 24.1%

3. Primary Outcome

Title	Overall Survival
Description	Time from date of treatment start until date of death due to any cause or last Follow-up.
Time Frame	Up to 97 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/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. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	29
Median (Full Range) [Weeks]	14

4. Primary Outcome

Title	Event-free Survival
Description	Time from date of treatment start until the date of first objective documentation of disease-relapse.
Time Frame	Up to 21 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/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. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	29
Median (Full Range) [Weeks]	5

5. Secondary Outcome

Title	Biomarker Expressions
Description	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.
Time Frame	Up to 30 days

Outcome Measure Data

Analysis Population Description

Samples and data required for the above outcome measure were not done, therefore we cannot report any outcomes for the above outcome measure.

Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/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. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
Measure Participants	0

Adverse Events

Time Frame	1 year
Arm/Group Title	Treatment (Erlotinib Hydrochloride)
Arm/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. Erlotinib Hydrochloride: Given PO Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events
Total	6/29 (20.7%)
Serious Adverse Events
	Treatment (Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events
Total	23/29 (79.3%)
Blood and lymphatic system disorders
Blood and Lymphatic System disorder - other	1/29 (3.4%)	1
Gastrointestinal disorders
Diarrhea	3/29 (10.3%)	3
Espohageal Ulcer	1/29 (3.4%)	1
Nausea	1/29 (3.4%)	1
Oral Mucositis	1/29 (3.4%)	1
General disorders
Death	3/29 (10.3%)	3
Fatigue	3/29 (10.3%)	3
Fever	3/29 (10.3%)	3
Pain	1/29 (3.4%)	2
Infections and infestations
Lung Infection	9/29 (31%)	10
Neutropenic Fever	5/29 (17.2%)	8
Sepsis	3/29 (10.3%)	4
Metabolism and nutrition disorders
Hyperbilirubinemia	1/29 (3.4%)	1
Tumor Lysis Syndrome	1/29 (3.4%)	1
Nervous system disorders
Seizure	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Pleuritic Pain	1/29 (3.4%)	1
Skin and subcutaneous tissue disorders
Skin Infection	1/29 (3.4%)	1
Vascular disorders
Hematoma	1/29 (3.4%)	1
Hypotension	1/29 (3.4%)	1
Thromboembolic Event	1/29 (3.4%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Erlotinib Hydrochloride)
	Affected / at Risk (%)	# Events
Total	29/29 (100%)
Eye disorders
Watery eyes	5/29 (17.2%)	5
Gastrointestinal disorders
Diarrhea	10/29 (34.5%)	10
Nausea	8/29 (27.6%)	8
General disorders
Fatigue	10/29 (34.5%)	10
Edema	5/29 (17.2%)	5
Infections and infestations
Pneumonia	14/29 (48.3%)	14
Neutropenic Fever	13/29 (44.8%)	13
Musculoskeletal and connective tissue disorders
Muscle Aches	5/29 (17.2%)	5
Nervous system disorders
Dizziness	4/29 (13.8%)	4
Respiratory, thoracic and mediastinal disorders
Shortness of breath	11/29 (37.9%)	11
Skin and subcutaneous tissue disorders
Rash	7/29 (24.1%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.