Daunorubicin and Cytarabine With or Without Uproleselan in Treating Older Adult Patients With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy
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|ClinicalTrials.gov Identifier: NCT03701308|
Recruitment Status : Recruiting
First Posted : October 10, 2018
Last Update Posted : July 16, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Cytarabine Drug: Daunorubicin Drug: Uproleselan||Phase 2 Phase 3|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||670 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized Phase II/III Study of Conventional Chemotherapy +/- Uproleselan (GMI-1271) in Older Adults With Acute Myeloid Leukemia Receiving Intensive Induction Chemotherapy|
|Actual Study Start Date :||January 16, 2019|
|Estimated Primary Completion Date :||December 1, 2025|
|Estimated Study Completion Date :||December 1, 2025|
Active Comparator: Group I (daunorubicin, cytarabine)
INDUCTION: Patients receive daunorubicin IV on days 1-3 and cytarabine via CIVI over 168 hours on days 1-7. Patients with residual disease indicated by bone marrow examination receive a second induction including daunorubicin IV on days 1-3 and cytarabine CIVI over 12 hours on days 1-5.
CONSOLIDATION: Patients receive cytarabine IV over 3 hours on days 1-5. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Experimental: Group II (uproleselan, daunorubicin, cytarabine)
INDUCTION: Patients receive uproleselan IV QD on day 1 and then every 12 hours on days 2-10. Patients also receive daunorubicin IV on days 2-4 and cytrarabine CIVI over 168 hours on days 2-8 over 168 hours. Patients with residual disease indicated by bone marrow examination receive a second induction including uprleselan IV QD on day 1 and then every 12 hours on days 2-10, daunorubicin IV on days 2-3, and cytarabine CIVI over 120 hours on days 2-6.
CONSOLIDATION: Patients who achieve a CR or CRi receive uproleselan IV QD on day 1 and every 12 hours on days 2-8 and cytarabine IV over 3 hours on days 2-6. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
Other Name: GMI-1271
- Event-free survival (EFS) (Phase II) [ Time Frame: Up to 5 years ]EFS is defined as the time from the date of registration/randomization to the first of failure to achieve a complete remission (CR) during induction, relapse, or death due to any cause, with patients last known to be alive and event-free censored at the date of last contact.
- Overall survival (OS) (Phase III) [ Time Frame: Up to 5 years ]Will be measured from the date of registration/randomization to death from any cause, with patients last known to be alive censored at the date of last contact.
- EFS rate [ Time Frame: Up to 1 year ]Will be formally tested hierarchically in a confirmatory setting at an overall one sided alpha of 0.025 level at the same time as the primary endpoint. Both hazard ratio and p-value for EFS will be presented.
- Impact of off-protocol transplantation [ Time Frame: Up to 5 years ]Sensitivity analyses will be conducted. In addition, the proportion of patients who received transplantation in the two arms will be summarized and compared using a chi-square test.
- Consistency of the treatment effect among each subgroup [ Time Frame: From baseline up to 5 years ]Non-parametric methods such as Kaplan-Meier and log-rank tests will be used within each subgroup. Univariate/multivariate Cox models will be fit within each subgroups; hazard ratios will be used to quantify the treatment effect within each subgroup, along with the 95% confidence intervals.
- Disease-free survival (DFS) [ Time Frame: Time from achieving a complete response to time of relapse or death, assessed up to 5 years ]
- Complete remission (CR) and overall response rate [ Time Frame: Up to 5 years ]
- Incidence of adverse events [ Time Frame: Up to 5 years ]Will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 5.0. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
- Prediction of CR, EFS, DFS, and OS by pretreatment characteristics such as age, morphology, cytogenetics, immunophenotype, molecular genetic features, WBC count and hemogram, and performance status with clinical outcomes [ Time Frame: Up to 5 years ]The associations between these baseline factors and CR, EFS, DFS, and OS will be analyzed using Kaplan-Meier curves, log-rank test, contingency table and chi-square test whenever appropriate. Multivariable analysis including Cox proportional hazards models and logistic regression models will be used as well to evaluate the associations.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03701308
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|Principal Investigator:||Geoffrey L Uy||Alliance for Clinical Trials in Oncology|