Erlotinib Study for Myelodysplastic Syndrome (MDS)

Phase 2

Completed

Conditions: Myelodysplastic Syndrome

Interventions: Drug: Erlotinib

Registration Number: NCT00977548

Lead Sponsor: H. Lee Moffitt Cancer Center and Research Institute

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).

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 39

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Erlotinib Treatment	Erlotinib	Erlotinib was given as an oral 150 mg daily dose for 16 weeks. The dose was adjusted for diarrhea, rash and pulmonary toxicity.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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.