Myelodysplastic Syndrome
Conditions
Keywords
MDS, blood diseases, bone marrow, hematopoietic, leukemia
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.
Interventions
DRUGErlotinib
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.
Sponsors
Genentech, Inc.
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Between September 2009 and January 2011, 39 patients signed consent at Moffitt Cancer Center.
Pre-assignment details
4 of the initial 39 patients were found to be ineligible after signing informed consent.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 8 |
| Overall Study | Ineligible | 4 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Erlotinib Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 34 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age Continuous | 73 years |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 32 / 35 |
| serious Total, serious adverse events | 24 / 35 |
Outcome results
Primary
Combined Overall Response Rate (ORR)
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
Population: All evaluable participants. Nine patients were not evaluable for response (withdrew consent or off study due to adverse event before first evaluation).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Erlotinib Treatment | Combined Overall Response Rate (ORR) | Marrow Complete Response (CR) | 3 participants |
| Erlotinib Treatment | Combined Overall Response Rate (ORR) | Hematological Improvement (HI) | 2 participants |
| Erlotinib Treatment | Combined Overall Response Rate (ORR) | Combined Overall Response | 5 participants |
Secondary
Leukemia Free Survival (LFS)
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
Population: All evaluable participants. Nine patients were not evaluable for response (withdrew consent or off study due to adverse event before first evaluation).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib Treatment | Leukemia Free Survival (LFS) | 5 months |
Secondary
Median Overall Survival (OS)
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
Population: All evaluable participants. Nine patients were not evaluable for response (withdrew consent or off study due to adverse event before first evaluation).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib Treatment | Median Overall Survival (OS) | 6.8 months |
Secondary
Median Progression Free Survival (PFS)
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
Population: All evaluable participants. Nine patients were not evaluable for response (withdrew consent or off study due to adverse event before first evaluation).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Erlotinib Treatment | Median Progression Free Survival (PFS) | 3.6 months |