Erlotinib Study for Myelodysplastic Syndrome (MDS)

This study has been completed.
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute Identifier:
First received: September 14, 2009
Last updated: September 13, 2013
Last verified: May 2013

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 Intervention Phase
Myelodysplastic Syndrome
Drug: Erlotinib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Combined Overall Response Rate (ORR) [ Time Frame: Up to 21 Months ] [ Designated as safety issue: No ]
    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:
  • Median Overall Survival (OS) [ Time Frame: Up to 21 Months ] [ Designated as safety issue: No ]
    OS: The time from randomization until death from any cause. Kaplan-Meier estimates were used for secondary endpoint analysis.

  • Median Progression Free Survival (PFS) [ Time Frame: Up to 21 Months ] [ Designated as safety issue: No ]
    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.

  • Leukemia Free Survival (LFS) [ Time Frame: Up to 21 Months ] [ Designated as safety issue: No ]
    LFS: Survival without evidence of relapse at any time post-transplant. Kaplan-Meier estimates were used for secondary endpoint analysis.

Enrollment: 39
Study Start Date: September 2009
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its identifier: NCT00977548

United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Principal Investigator: Rami Komrokji, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute Identifier: NCT00977548     History of Changes
Other Study ID Numbers: MCC-15961, OSI3666s
Study First Received: September 14, 2009
Results First Received: June 26, 2013
Last Updated: September 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
blood diseases
bone marrow

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions processed this record on April 15, 2014