A Phase 2 Trial of MLN8237 in Adult Participants With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome
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|ClinicalTrials.gov Identifier: NCT00830518|
Recruitment Status : Completed
First Posted : January 28, 2009
Results First Posted : May 11, 2018
Last Update Posted : May 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myelogenous Leukemia High-Grade Myelodysplastic Syndrome||Drug: Alisertib||Phase 2|
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have acute myeloid leukemia (AML) or high-grade myelodysplastic syndrome (MDS). This study looked at the antitumor activity in people who received alisertib.
The study enrolled 57 patients. Participants were categorized by disease sub-types AML and MDS. Participants received:
• Alisertib 50 mg
All participants took alisertib capsules every 12 hours each day for 7 days followed by a 14-day rest period in 21-day cycles for approximately 26 cycles.
This multi-center trial was conducted in North America and France. The overall time to participate in this study was until there is evidence of disease progression or unacceptable treatment-related toxicity. The participant could continue treatment beyond 12 months if it was considered by the Sponsor and the Investigator that they would derive benefit from continued alisertib treatment. Participants had weekly blood work and clinic visits, with disease assessments every 2 cycles (ie. every 6 weeks) up to and including Cycle 16. Reduced visits (every 12 weeks) were conducted for participants tolerating treatment beyond Cycle 16 and for participants off treatment without disease progression.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||57 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Trial of MLN8237, an Oral Aurora A Kinase Inhibitor, in Adult Patients With Acute Myelogenous Leukemia and High-Grade Myelodysplastic Syndrome|
|Actual Study Start Date :||February 10, 2009|
|Actual Primary Completion Date :||February 2, 2010|
|Actual Study Completion Date :||July 4, 2011|
Alisertib 50 mg, capsules, orally, twice daily for 7 days, followed by 14-day washout period, in 21-day cycles until disease progression or unacceptable treatment-related toxicity (Up to 26 Cycles).
Other Name: MLN8237
- Best Overall Response Rate (ORR) Based on Investigator's Assessment [ Time Frame: Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years) ]Best ORR is defined as the number of participants with complete remission(CR) or partial remission(PR) assessed by the Investigator using modified AML/MDS International Working Group(IWG) Criteria. AML:CR=neutrophils >1x10^9/L, platelets >100x10^9/L, bone marrow blasts(BMB) <5%, transfusion independent, no extramedullary disease(EMD); CRi=BMB <5%, transfusion independent, no EMD; PR=neutrophils >1x10^9/L, platelets >100x10^9/L, BMB >50% decrease and 5% to 25%, blasts <5% with Auer rods; PRi=BMB >50% decrease and 5% to 25%. MDS:CR=bone marrow: ≤5% myeloblasts with normal maturation, peripheral blood: hemoglobin ≥11 g/dL, platelets ≥100x10^9/L, neutrophils ≥1.0x10^9/L, blasts 0%; PR=all CR criteria if abnormal before treatment except: BMB decreased by ≥50% over pretreatment but still >5%; PRi=BMB decreased by ≥50% over pretreatment but still >5%; Marrow CR=bone marrow: ≤5% myeloblasts and decrease by ≥50% over pretreatment, peripheral blood hematologic improvement responses noted.
- Progression Free Survival (PFS) [ Time Frame: Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years) ]PFS is defined as the time from the date of first study drug administration to the date of first documented progressive disease (PD) or death.
- Duration of Response (DOR) [ Time Frame: Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years) ]Duration of response is defined as the time from the date of first documentation of a response to the date of first documented PD.
- Best Overall Hematologic Improvement (HI) Response for Myelodysplastic Syndrome Based on Investigator Assessment [ Time Frame: Baseline and every 2 cycles up to Cycle 16 (up to Month 12), from Cycle 17 every 4 cycles until disease progression, after end of treatment every 12 weeks for up to 12 Months (Approximately 2.4 years) ]Best overall HI response is defined as percentage of participants with response as assessed by Investigator based on IWG criteria: 1)Erythroid response (pretreatment,<11 g/dL): hemoglobin (Hgb) increase by ≥1.5 g/dL, relevant reduction of units of red blood cell (RBC) transfusions by absolute number of at least 4 RBC transfusions/8 weeks compared to pretreatment transfusion number in previous 8 weeks. Only RBC transfusions given for Hgb of ≤9.0 g/dL pretreatment will count in RBC transfusion response evaluation. 2)Platelet response (pretreatment,<100x10^9/L):Absolute increase of ≥30x10^9/L for participants starting->20x10^9/L platelets, increase <20x10^9/L to >20x10^9/L by at least 100%. 3)Neutrophil response (pretreatment,<1.0x10^9/L):At least 100% increase and an absolute increase >0.5x10^9/L. 4)Progression or relapse after HI:At least 1 of following: 50% decrement from maximum response levels in granulocytes or platelets, or reduction in Hgb by ≥1.5 g/dL, or transfusion dependence.
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Deaths [ Time Frame: First dose of study drug to 30 days after last dose (Up to 18.9 months) ]An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug was determined by the Investigator.
- Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events [ Time Frame: First dose of study drug to 30 days after last dose (Up to 18.9 months) ]Vital signs measurements (blood pressure, heart rate, and oral temperature) were obtained throughout the study. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
- Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events [ Time Frame: First dose of study drug to 30 days after last dose (Up to 18.9 months) ]Abnormal Laboratory Values for Chemistry or Hematology tests that were assessed by the investigator to be Grade 3 or higher using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. A treatment--emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00830518
|United States, New Jersey|
|Hematology and Oncology Associates of Northern New Jersey|
|Morristown, New Jersey, United States, 07962|
|Study Director:||Medical Director Clinical Science||Takeda|