Phase II Study Evaluating the Role of Erlotinib an Epidermal Growth Factor Receptor (EGFR) Inhibitor in the Treatment of Myelodysplastic Syndrome
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 39
- Locations
- 1
- Primary Endpoint
- Combined Overall Response Rate (ORR)
Study Overview
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.
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).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- 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
- •Therefore, if a test is done on a Monday, the Monday four weeks later would be considered Day
- •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.
Arms & Interventions
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.
Intervention: Erlotinib (Drug)
Outcomes
Primary Outcomes
Combined Overall Response Rate (ORR)
Time Frame: 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 Outcomes
- Median Overall Survival (OS)(Up to 21 Months)
- Median Progression Free Survival (PFS)(Up to 21 Months)
- Leukemia Free Survival (LFS)(Up to 21 Months)