Erlotinib Study for Myelodysplastic Syndrome (MDS)

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00977548
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 39
• Location: 1
• Arm: 1
• Duration (Months): 33
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to find out what effects, good and/or bad, erlotinib has on the patient and their myelodysplastic syndrome. Erlotinib has been approved by the Food and Drug Administration (FDA) to treat non-small cell lung cancer; however, erlotinib use in this study is considered investigational as the FDA has not approved it for the treatment of myelodysplastic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome	Drug: Erlotinib	Phase 2

Detailed Description

Screening Period: Informed consent, physical examination, medical history report, blood tests, pregnancy test (if applicable), list of current medications, description of symptoms, chest x-ray, ECG, bone marrow aspirate/biopsy within 4 weeks of study start.

Weeks 2,6,10 and 14: Blood tests.

Weeks 4 and 12: Blood tests, physical exam, patients will answer question about how they are feeling and if there are any changes to medication they have taken.

Weeks 8 and 16: Blood tests, physical exam, patients will answer question about how they are feeling and if there are any changes to medication they have taken, bone marrow aspirate/biopsy (if physician has determined the patient has had a clinical response or partial response to treatment.

After week 16 (if responding to treatment): Have a bone marrow aspirate/biopsy (will be repeated at time of relapse, i.e., more than 50% increase in the percentage of myeloblasts [leukemia cells] or drop in blood counts after they improved or requiring regular blood transfusions after not requiring them for at least 8 weeks, or after 1 year in study).

After the patient has stopped taking erlotinib: Periodic follow-up on patients' status.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study Evaluating the Role of Erlotinib an Epidermal Growth Factor Receptor (EGFR) Inhibitor in the Treatment of Myelodysplastic Syndrome
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Erlotinib Treatment Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.	Drug: Erlotinib; Participants took erlotinib at least 1 hour before, or 2 hours after they ate a meal or snack. Participants were advised to take erlotinib at around the same time every day.; Other Names: Tarceva OSI-774

Outcome Measures

Primary Outcome Measures

1. Combined Overall Response Rate (ORR) [Up to 21 Months]

   Best Response Categories: Marrow complete response (CR), Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment; Hematological improvement (HI), Hgb increase by ≥ 1.5 g/dL, Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L, At least 100% increase and an absolute increase of > 0.5 x 10^9/L, as defined by the International Working Group (IWG) 2006 criteria.

Secondary Outcome Measures

1. Median Overall Survival (OS) [Up to 21 Months]

   OS: The time from randomization until death from any cause. Kaplan-Meier estimates were used for secondary endpoint analysis.

2. Median Progression Free Survival (PFS) [Up to 21 Months]

   PFS: The time elapsed between treatment initiation and tumor progression or death from any cause. Kaplan-Meier estimates were used for secondary endpoint analysis. Disease Progression is defined using International Working Group (IWG) Response Criteria for MDS, as at least 50% decrement from maximum remission/response levels in granulocytes or platelets; reduction in hemoglobin (Hgb) concentration by ≥ 2 g/dL; transfusion dependence.

3. Leukemia Free Survival (LFS) [Up to 21 Months]

   LFS: Survival without evidence of relapse at any time post-transplant. Kaplan-Meier estimates were used for secondary endpoint analysis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients must have an established diagnosis of myelodysplastic syndrome (MDS) and have either: Low or intermediate 1 risk disease by International Prognostic Scoring System (IPSS) for MDS with symptomatic anemia (defined as hemoglobin less than 10.0 g/dl) or transfusion dependent anemia (defined as requiring ≥ 4 units of red blood cells (RBCs) administered with a pretreatment hemoglobin value of ≤ 9 g/dL in the 8 weeks prior to Day 1 of treatment in this study). Patients with anemia must have no response to at least to 6 weeks trial of erythroid stimulating agents (ESA) [erythropoietin/ darbepoetin]. Patients with serum erythropoietin levels more than 500 mU/ ml on diagnosis are eligible to the study without erythropoietin/darbepoetin prior treatment. Patients who do not meet anemia criteria are still eligible if they had thrombocytopenia with two or more platelet counts < 50 x 10^{9/L or a significant clinical hemorrhage requiring platelet transfusions or if they had neutropenia with an absolute neutrophil count (ANC) < 1 x 10}9/L; Intermediate-2 or high risk MDS by IPSS.

• Patients ≥ 60 years with Acute Myeloid Leukemia (AML) by WHO classification and myeloblasts percentage 20-30% (RAEB-t by MDS French-American-British (FAB) classification) are eligible for the study if deemed not suitable for induction chemotherapy or declined that option.

• All prior treatment must have been discontinued 28 days prior to Day 1 of treatment in this study except (ESA) and colony stimulating factors where it should be stopped 14 days prior to start therapy on study, and hydroxyurea should be stopped 2 days before.

• Prior bone marrow or stem cell transplant is allowed.

• Secondary or therapy related MDS patients are eligible.

• Patients with chronic myelomonocytic leukemia (CMML) are eligible.

• Patients must have a performance status of 0 - 2 by Zubrod performance status criteria.

• Pretreatment pathology materials must be available for morphologic review. Collection of blood and marrow specimens for pathology review must be completed within 28 days prior to registration.

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for at least 2 years.

• In calculating days of tests and measurements, the day a test or measurement is done is considered Day 0. Therefore, if a test is done on a Monday, the Monday four weeks later would be considered Day 28. This allows for efficient patient scheduling without exceeding the guidelines. If Day 28 or 60 falls on a weekend or holiday, the limit may be extended to the next working day.

• All patients must be informed of the investigational nature of this study and must sign and give written consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

• Patients must not have received prior remission induction chemotherapy as treatment for MDS.

• Patients must not be pregnant or nursing because of the potential risks of the drugs used in this study. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

• Patients who are known HIV positive are not eligible for this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida	United States	33612

Sponsors and Collaborators

• H. Lee Moffitt Cancer Center and Research Institute
• Genentech, Inc.

Investigators

• Principal Investigator: Rami Komrokji, M.D., H. Lee Moffitt Cancer Center and Research Institute

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Moffitt Cancer Center Clinical Trials website

Publications

None provided.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT00977548
• Other Study ID Numbers: MCC-15961; OSI3666s
• First Posted: Sep 15, 2009
• Last Update Posted: Sep 16, 2013
• Last Verified: May 1, 2013

• Keywords provided by H. Lee Moffitt Cancer Center and Research Institute: MDS; blood diseases; bone marrow; hematopoietic; leukemia
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Syndrome; Erlotinib Hydrochloride

Study Results

Participant Flow

Recruitment Details	Between September 2009 and January 2011, 39 patients signed consent at Moffitt Cancer Center.
Pre-assignment Detail	4 of the initial 39 patients were found to be ineligible after signing informed consent.

Arm/Group Title	Erlotinib Treatment
Arm/Group Description	Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.
Period Title: Overall Study
STARTED	39
COMPLETED	26
NOT COMPLETED	13

Baseline Characteristics

Arm/Group Title	Erlotinib Treatment
Arm/Group Description	Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.
Overall Participants	35
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 2.9%
>=65 years	34 97.1%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	73
Sex: Female, Male (Count of Participants)
Female	7 20%
Male	28 80%
Region of Enrollment (participants) [Number]
United States	35 100%

Outcome Measures

1. Primary Outcome

Title	Combined Overall Response Rate (ORR)
Description	Best Response Categories: Marrow complete response (CR), Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment; Hematological improvement (HI), Hgb increase by ≥ 1.5 g/dL, Absolute increase of ≥ 30 x 10^9/L for patients starting with > 20 x 10^9/L, At least 100% increase and an absolute increase of > 0.5 x 10^9/L, as defined by the International Working Group (IWG) 2006 criteria.
Time Frame	Up to 21 Months

Outcome Measure Data

Analysis Population Description

All evaluable participants. Nine patients were not evaluable for response (withdrew consent or off study due to adverse event before first evaluation).

Arm/Group Title	Erlotinib Treatment
Arm/Group Description	Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.
Measure Participants	26
Marrow Complete Response (CR)	3 8.6%
Hematological Improvement (HI)	2 5.7%
Combined Overall Response	5 14.3%

2. Secondary Outcome

Title	Median Overall Survival (OS)
Description	OS: The time from randomization until death from any cause. Kaplan-Meier estimates were used for secondary endpoint analysis.
Time Frame	Up to 21 Months

Outcome Measure Data

Analysis Population Description

All evaluable participants. Nine patients were not evaluable for response (withdrew consent or off study due to adverse event before first evaluation).

Arm/Group Title	Erlotinib Treatment
Arm/Group Description	Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.
Measure Participants	26
Median (95% Confidence Interval) [months]	6.8

3. Secondary Outcome

Title	Median Progression Free Survival (PFS)
Description	PFS: The time elapsed between treatment initiation and tumor progression or death from any cause. Kaplan-Meier estimates were used for secondary endpoint analysis. Disease Progression is defined using International Working Group (IWG) Response Criteria for MDS, as at least 50% decrement from maximum remission/response levels in granulocytes or platelets; reduction in hemoglobin (Hgb) concentration by ≥ 2 g/dL; transfusion dependence.
Time Frame	Up to 21 Months

Outcome Measure Data

Analysis Population Description

All evaluable participants. Nine patients were not evaluable for response (withdrew consent or off study due to adverse event before first evaluation).

Arm/Group Title	Erlotinib Treatment
Arm/Group Description	Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.
Measure Participants	26
Median (95% Confidence Interval) [months]	3.6

4. Secondary Outcome

Title	Leukemia Free Survival (LFS)
Description	LFS: Survival without evidence of relapse at any time post-transplant. Kaplan-Meier estimates were used for secondary endpoint analysis.
Time Frame	Up to 21 Months

Outcome Measure Data

Analysis Population Description

All evaluable participants. Nine patients were not evaluable for response (withdrew consent or off study due to adverse event before first evaluation).

Arm/Group Title	Erlotinib Treatment
Arm/Group Description	Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.
Measure Participants	26
Median (95% Confidence Interval) [months]	5

Adverse Events

Time Frame	1 year, 9 months
Arm/Group Title	Erlotinib Treatment
Arm/Group Description	Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.
All Cause Mortality
	Erlotinib Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Erlotinib Treatment
	Affected / at Risk (%)	# Events
Total	24/35 (68.6%)
Blood and lymphatic system disorders
Hemoglobin	10/35 (28.6%)
Neutrophils/granulocytes (ANC/AGC)	1/35 (2.9%)
Platelets	5/35 (14.3%)
Coagulation - Other	1/35 (2.9%)
Cardiac disorders
Cardiac Arrhythmia - Other	1/35 (2.9%)
Cardiac ischemia/infarction	1/35 (2.9%)
Hypotension	1/35 (2.9%)
Gastrointestinal disorders
Anorexia	3/35 (8.6%)
Diarrhea	5/35 (14.3%)
Ileus, GI (functional obstruction of bowel, i.e., neuroconstipation)	1/35 (2.9%)
Hemorrhage, GI - Colon	2/35 (5.7%)
Hemorrhage, GI - Lower GI NOS	1/35 (2.9%)
General disorders
Fatigue (asthenia, lethargy, malaise)	4/35 (11.4%)
Fever (in the absence of neutropenia)	2/35 (5.7%)
Death not associated with CTCAE term - Death NOS	3/35 (8.6%)
Death not associated with CTCAE term - Disease progression NOS	2/35 (5.7%)
Death not associated with CTCAE term - Sudden death	1/35 (2.9%)
Hemorrhage/Bleeding - Other	1/35 (2.9%)
Neurology - Other	2/35 (5.7%)
Syncope (fainting)	1/35 (2.9%)
Pain - Abdomen NOS	1/35 (2.9%)
Pain - Back	1/35 (2.9%)
Pain - Chest wall	1/35 (2.9%)
Pain - Head/headache	1/35 (2.9%)
Pain - Other	1/35 (2.9%)
Pain - Throat/pharynx/larynx	1/35 (2.9%)
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Abdomen NOS	1/35 (2.9%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils -Blood	1/35 (2.9%)
Infection (documented clinically or microbiologically) w/Grade 3 or 4 neutrophils - Lung (pneumonia)	2/35 (5.7%)
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils - Mucosa	1/35 (2.9%)
Infection - Other	8/35 (22.9%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Blood	3/35 (8.6%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	2/35 (5.7%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus	1/35 (2.9%)
Infection with unknown ANC - Lung (pneumonia)	1/35 (2.9%)
Metabolism and nutrition disorders
Creatinine	1/35 (2.9%)
Sodium, serum-high (hypernatremia)	1/35 (2.9%)
Uric acid, serum-high (hyperuricemia)	1/35 (2.9%)
Nervous system disorders
Hemorrhage, CNS	2/35 (5.7%)
Psychiatric disorders
Mental status	1/35 (2.9%)
Mood alteration - Depression	1/35 (2.9%)
Renal and urinary disorders
Renal failure	3/35 (8.6%)
Respiratory, thoracic and mediastinal disorders
Cough	2/35 (5.7%)
Dyspnea (shortness of breath)	6/35 (17.1%)
Pulmonary/Upper Respiratory - Other	1/35 (2.9%)
Skin and subcutaneous tissue disorders
Rash: acne/acneiform	1/35 (2.9%)
Vascular disorders
Thrombosis/embolism (vascular access-related)	1/35 (2.9%)
Thrombosis/thrombus/embolism	1/35 (2.9%)
Vascular - Other	1/35 (2.9%)
Other (Not Including Serious) Adverse Events
	Erlotinib Treatment
	Affected / at Risk (%)	# Events
Total	32/35 (91.4%)
Blood and lymphatic system disorders
Platelets	4/35 (11.4%)
Hemoglobin	2/35 (5.7%)
Neutrophils/granulocytes (ANC/AGC)	2/35 (5.7%)
Edema: limb	2/35 (5.7%)
Lymphatics - Other	2/35 (5.7%)
Eye disorders
Dry eye syndrome	2/35 (5.7%)
Gastrointestinal disorders
Diarrhea	23/35 (65.7%)
Anorexia	14/35 (40%)
Nausea	6/35 (17.1%)
Gastrointestinal - Other	3/35 (8.6%)
Vomiting	3/35 (8.6%)
Dry mouth/salivary gland (xerostomia)	2/35 (5.7%)
Hemorrhoids	2/35 (5.7%)
Hemorrhage, GI - Colon	2/35 (5.7%)
Hemorrhage, GI - Lower GI NOS	2/35 (5.7%)
General disorders
Fatigue (Asthenia, lethargy, malaise)	17/35 (48.6%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10^9/L)	3/35 (8.6%)
Sweating (diaphoresis)	2/35 (5.7%)
Weight loss	2/35 (5.7%)
Hemorrhage/Bleeding - Other	6/35 (17.1%)
Pain - Chest/thorax NOS	2/35 (5.7%)
Pain - Other	2/35 (5.7%)
Pain - Scalp	2/35 (5.7%)
Dizziness	4/35 (11.4%)
Infections and infestations
Infection - Other	2/35 (5.7%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Lung (pneumonia)	2/35 (5.7%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Blood	2/35 (5.7%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Eye NOS	2/35 (5.7%)
Respiratory, thoracic and mediastinal disorders
Hemorrhage, pulmonary/upper respiratory - Nose	4/35 (11.4%)
Cough	6/35 (17.1%)
Dyspnea (shortness of breath)	7/35 (20%)
Skin and subcutaneous tissue disorders
Pruritus/itching	16/35 (45.7%)
Rash: acne/acneiform	15/35 (42.9%)
Dry skin	9/35 (25.7%)
Dermatology/Skin - Other	8/35 (22.9%)
Rash/desquamation	5/35 (14.3%)
Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)	2/35 (5.7%)
Ulceration	2/35 (5.7%)

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.