Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome
Conditions
Brief summary
The study tests the safety and efficacy of axitinib in patients who have the hematologic disease of Acute Myeloid Leukemia or Myelodysplastic Syndrome. The study tests patients who have poor prognosis before entering the study.
Interventions
patients were treated with axitinib at starting dose of 5 mg BID continuous dosing.
Sponsors
Pfizer
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
* Poor prognosis AML or MDS * Histological confirmation of diagnosis * White blood cell count less than or equal to 30,000/mm3 * Adequate hepatic and renal function documented within 14 days prior to registration * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * No evidence of preexisting uncontrolled hypertension * Not a suitable candidate for chemotherapy * No prior systemic chemotherapy treatment for AML or MDS or treatment with an anti-angiogenesis agent
Exclusion criteria
* Patients must not have
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Objective Response (OR) | Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 4 weeks up to 35 weeks | Participants with OR based on a assessment of confirmed complete remission (CR) or partial remission (PR) according to Cheson criteria for Acute myeloid leukemia (AML) and Myelodysplastic syndrome (MDS). CR: those with \> 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, \<5 % myeloblast cells for bone marrow with peripheral blood value lasting at least 1 month and 2 months for AML and MDS respectively. PR : those with all criteria for CR except 5-25 % blasts in bone marrow and at least 50% decrease in blast over pretreatment for AML and MDS respectively. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DR) | First documentation of objective response until objective disease progression or discontinuation from the study due to any cause assessed every 4 weeks up to 35 weeks | Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1). DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
| Bone Marrow Micro Vessel Density (MVD) | Day 1, Week 2 thereafter every 4 weeks up to 35 weeks | Bone marrow MVD in tumors is a measure of angiogenesis and a prognostic indicator that correlates with an increased risk of metastasis in various cancers and with overall and relapse free survival in participants with AML or MDS. Bone marrow biopsies and bone marrow clot samples were assessed for MVD (cluster of differentiation 31 \[CD31\] staining). |
| Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1) and VEFGR Receptor 2 (VEGFR-2) Phosphorylation | Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) | Vascular endothelial growth factor (VEGF) promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Mononuclear (MNC) cell VEGF receptor expression and phosphorylation was assessed by in situ western blot analysis. VEGFR-1 and VEGFR-2 evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot. |
| Percentage of Participants With Hematologic Improvement (HI) | Baseline, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) | HI was described by the number of individual and positively affected cell lines (Erythroid response, Platelet response, Neutrophil response). Improvements must last at least 2 months. |
| Population Pharmacokinetics of Axitinib (AG-013736) | Day 1 (pre-dose) and every 4 weeks up to 35 weeks | Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules. |
| Overall Survival (OS) | Baseline to death due to any cause or at least every 3 months after discontinuation of study treatment | Time in days from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1). Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact. |
| Plasma Vascular Endothelial Growth Factor (VEGF) Concentration | Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose) | VEGF promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Plasma VEGF concentration evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Axitinib Axitinib (AG-013736) tablet administered orally at a dose of 5 milligram (mg) twice daily (BID) continuously. Treatment was administered continuously until progression, relapse, failure, or disease transformation or toxicity occurred. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 7 |
| Overall Study | Other | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Axitinib |
|---|---|
| Age Continuous | 77.42 Years STANDARD_DEVIATION 8.53 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 12 |
| serious Total, serious adverse events | 9 / 12 |
Outcome results
Primary
Percentage of Participants With Objective Response (OR)
Participants with OR based on a assessment of confirmed complete remission (CR) or partial remission (PR) according to Cheson criteria for Acute myeloid leukemia (AML) and Myelodysplastic syndrome (MDS). CR: those with \> 20% cellularity of bone marrow biopsy, no presence of extramedullary leukemia for AML, \<5 % myeloblast cells for bone marrow with peripheral blood value lasting at least 1 month and 2 months for AML and MDS respectively. PR : those with all criteria for CR except 5-25 % blasts in bone marrow and at least 50% decrease in blast over pretreatment for AML and MDS respectively.
Time frame: Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 4 weeks up to 35 weeks
Population: Study Population included all participants who received at least 1 dose of study medication and had a baseline assessment of disease.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Axitinib | Percentage of Participants With Objective Response (OR) | 0 Percentage of participants |
Secondary
Bone Marrow Micro Vessel Density (MVD)
Bone marrow MVD in tumors is a measure of angiogenesis and a prognostic indicator that correlates with an increased risk of metastasis in various cancers and with overall and relapse free survival in participants with AML or MDS. Bone marrow biopsies and bone marrow clot samples were assessed for MVD (cluster of differentiation 31 \[CD31\] staining).
Time frame: Day 1, Week 2 thereafter every 4 weeks up to 35 weeks
Population: Data was not summarized for this particular endpoint due to lack of efficacy.
Secondary
Duration of Response (DR)
Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1). DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time frame: First documentation of objective response until objective disease progression or discontinuation from the study due to any cause assessed every 4 weeks up to 35 weeks
Population: Analysis for this particular endpoint was not conducted due to lack of efficacy.
Secondary
Overall Survival (OS)
Time in days from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1). Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.
Time frame: Baseline to death due to any cause or at least every 3 months after discontinuation of study treatment
Population: Analysis for this particular endpoint was not conducted due to lack of efficacy.
Secondary
Percentage of Participants With Hematologic Improvement (HI)
HI was described by the number of individual and positively affected cell lines (Erythroid response, Platelet response, Neutrophil response). Improvements must last at least 2 months.
Time frame: Baseline, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)
Population: Analysis for this particular endpoint was not conducted due to lack of efficacy.
Secondary
Plasma Vascular Endothelial Growth Factor (VEGF) Concentration
VEGF promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Plasma VEGF concentration evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot.
Time frame: Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)
Population: Data was not summarized for this particular endpoint due to lack of efficacy.
Secondary
Population Pharmacokinetics of Axitinib (AG-013736)
Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time frame: Day 1 (pre-dose) and every 4 weeks up to 35 weeks
Secondary
Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1) and VEFGR Receptor 2 (VEGFR-2) Phosphorylation
Vascular endothelial growth factor (VEGF) promotes cancer progression by inducing angiogenesis via VEGF receptors, signals directly through receptors VEGFR-1 and VEGFR-2. Change in biomarkers related to VEGFR signal transduction pathways after axitinib treatment was assessed. Mononuclear (MNC) cell VEGF receptor expression and phosphorylation was assessed by in situ western blot analysis. VEGFR-1 and VEGFR-2 evaluations were performed using samples from peripheral blood plasma, bone marrow aspirate, bone marrow (Core) biopsy and bone marrow clot.
Time frame: Day 1, Week 2 thereafter every 4 weeks up to 35 weeks and follow up (at least 30 days after last dose)
Population: Data was not summarized for this particular endpoint due to lack of efficacy.