Phase II Trial of Alisertib With Induction Chemotherapy in High-risk AML
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|ClinicalTrials.gov Identifier: NCT02560025|
Recruitment Status : Active, not recruiting
First Posted : September 25, 2015
Results First Posted : October 11, 2018
Last Update Posted : August 22, 2019
This research study is studying a targeted therapy (a form of treatment that uses drugs or other substances to identify and attack specific types of cancer cells with less harm to normal cells) as a possible treatment for high-risk acute myeloid leukemia.
The names of the study interventions involved in this study are:
- Alisertib / MLN8237
- Cytarabine / Cytosine Arabinoside
- Idarubicin / Idarubicin hydrochloride
- Daunorubicin (Can be used in place of idarubicin)
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Alisertib Drug: Cytarabine Drug: Idarubicin Drug: Daunorubicin||Phase 2|
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
As part of this research study, the participant will take alisertib in combination with conventional chemotherapies, idarubicin and cytarabine. Alisertib has not been approved by the FDA (U.S. Food and Drug Administration) for acute myeloid leukemia (AML). However, cytarabine and idarubicin have both been approved by the FDA for treatment of AML. It also means that the FDA (U.S. Food and Drug Administration) has not approved giving alisertib with idarubicin and cytarabine for use in participants, including participants with this type of cancer.
Earlier pre-clinical studies and clinical trials have suggested the alisertib may have clinical promise as a single agent in acute myeloid leukemia. Alisertib is a selective small molecule inhibitor of Aurora A kinase, an enzyme which may play a role in the survival of leukemia cells. Alisertib is being studied for the treatment of advanced malignancies, including AML. Essentially, this means that alisertib may work to halt the growth of malignancy (abnormal cells dividing without control and invading nearby tissues) through a targeted mechanism. By combining alisertib with standard chemotherapy, the hope is to enhance the efficacy of current treatment used for acute myeloid leukemia. An earlier study of this combination has completed accrual, and demonstrated that the regimen is well tolerated.
Through this study, the investigators would like to determine if the addition of alisertib to standard 7+3 chemotherapy improves efficacy as measured by the rate of complete remission (a decreased or disappearance of signs and symptoms of cancer).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of the Aurora A Kinase Inhibitor Alisertib in Combination With 7+3 Induction Chemotherapy in Patients With High-risk Acute Myeloid Leukemia|
|Study Start Date :||December 2015|
|Actual Primary Completion Date :||October 2017|
|Estimated Study Completion Date :||February 2020|
Experimental: Alisertib / MLN8237
Participants will initially receive 7+3 induction chemotherapy, consisting of cytarabine and concurrent idarubicin (or daunorubicin if appropriate). Oral alisertib, at 30mg twice daily, will begin on day 8, and will continue for 7 days. During induction, patients with residual disease at day 14 may have re-induction with "5+2" chemotherapy, but will not receive additional dosing of alisertib at that time. Following count recovery after induction, if patients proceed to consolidative cycles of therapy with cytarabine, they will receive alisertib at day 6 following conclusion of cytarabine administration. Upon count recovery following consolidation, alisertib will be resumed for 7 days, followed by 14 days off, and will be continued as 21-day cycles of maintenance, for up to 12 cycles.
Other Name: MLN8237
Other Name: Cytosine Arabinoside
Other Name: Idarubicin hydrochloride
Can be used in place of idarubicin
Other Name: Cerubidine®
- Number of Participants That Achieved Complete Remission [ Time Frame: From the start of treatment until the end of study treatment, up to approximately 10 months ]
The number of participants that achieved a best overall response of complete remission while on study.
Complete remission (CR): Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/μL and a platelet count of 100,000/μL, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, existing extramedullary disease. If possible, at least one bone marrow biopsy should be performed to confirm CR.
- Number of Participants That Achieved Complete Remission With Incomplete Blood Count Recovery (CRi) [ Time Frame: From the start of treatment until the end of study treatment, up to approximately 10 months ]
The number of participants that achieved a best overall response of CRi while on study.
Complete Remission with Incomplete Blood Count Recovery (CRi): Same as for CR but without achievement of ANC at least 1000/uL (CRi) and/or platelet count of 100,000/uL (CRp).
- Overall Survival [ Time Frame: 1 Year ]
- Relapse Free Survival [ Time Frame: 1 Year ]
- Remission Duration [ Time Frame: 2 Years ]
- Number of Participants With Serious Adverse Events [ Time Frame: From the start of treatment until 30 days after the last dose of a study drug is received, up to approximately 11 months ]Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 4). Adverse events were considered to be Serious Adverse Events (SAE) if they were grade 3 or greater and deemed to be possibly, probably, or definitely related to the study treatment.
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): NCT02560025
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Amir Fathi, MD||Massachusetts General Hospital|