Venetoclax With Combination Chemotherapy in Treating Patients With Newly Diagnosed or Relapsed or Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03214562|
Recruitment Status : Recruiting
First Posted : July 11, 2017
Last Update Posted : June 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|High Risk Myelodysplastic Syndrome Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Cytarabine Biological: Filgrastim Drug: Fludarabine Drug: Fludarabine Phosphate Drug: Idarubicin Drug: Idarubicin Hydrochloride Biological: Pegfilgrastim Drug: Venetoclax||Phase 1 Phase 2|
I. To evaluate the safety and tolerability and to determine the dose-limiting toxicity and the maximum tolerated dose MTD of the combination of fludarabine phosphate (fludarabine), cytarabine, filgrastim (GCSF), idarubicin hydrochloride (idarubicin) (FLAG-IDA) + venetoclax for patients with acute myeloid leukemia (AML) (Phase 1b).
II. To determine the overall activity of this combination in patients newly diagnosed or relapsed/refractory (AML) (Phase 2).
I. Determine the preliminary assessment of efficacy by response to revised International Working Group (IWG) criteria and time to response variables including overall survival (OS), event-free survival (EFS) and duration of response (DOR).
II. Determine biomarkers that may be predictive of venetoclax activity.
OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study.
INDUCTION THERAPY: Patients receive venetoclax orally (PO) on days 1-14, fludarabine phosphate intravenously (IV) over 30 minutes on days 2-6, cytarabine IV over 4 hours on days 2-6, idarubicin hydrochloride IV over 15-30 minutes on days 4 and 5, filgrastim subcutaneously (SC) on days 1-7, or pegfilgrastim SC after day 5. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients receive venetoclax PO on days 1-7, fludarabine phosphate IV over 30 minutes on days 2-4, cytarabine IV over 4 hours on days 2-4, filgrastim SC on days 1-7, or pegfilgrastim SC after days 3. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive idarubicin hydrochloride as in Induction Therapy during 1 cycle of Consolidation Therapy per the treating physician.
MAINTENANCE THERAPY: Patients receive venetoclax PO on days 1-28. Cycles repeat every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up within 30 days.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||56 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1b/2 Study of the BCL-2 Inhibitor Venetoclax in Combination With Standard Intensive AML Induction/Consolidation Therapy With FLAG-IDA in Patients With Newly Diagnosed or Relapsed/Refractory AML|
|Actual Study Start Date :||September 26, 2017|
|Estimated Primary Completion Date :||September 30, 2023|
|Estimated Study Completion Date :||September 30, 2023|
Experimental: Treatment (venetoclax, FLAG-IDA)
See detailed description.
Other Name: Fluradosa
Drug: Fludarabine Phosphate
Drug: Idarubicin Hydrochloride
- Overall response rate (ORR) [ Time Frame: Up to 6 years ]Defined as complete response (CR) + CR with incomplete blood count recovery (CRi) + partial response (PR). Will be estimated along with the 95% credible interval.
- CR/CRi rate [ Time Frame: Up to 6 years ]Will be estimated along with the 95% credible interval.
- Hematologic response [ Time Frame: Up to 6 years ]Will be estimated along with the 95% credible interval.
- Duration of response [ Time Frame: From the date of initial response, assessed up to 6 years ]Defined as the number of days from the date of initial response (PR or better) to the date of first documented disease progression/relapse or death, whichever occurs first. Will be calculated for all patients.
- Event-free survival [ Time Frame: From the date of treatment initiation, assessed up to 6 years ]Defined as the number of days from the date of treatment initiation (i.e., course 1 day 1) to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first. Will be calculated for all patients. Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
- Overall survival [ Time Frame: Up to 6 years ]Estimated using Kaplan-Meier method. Log-rank tests will be used to compare among subgroups of patients.
- Anti-tumor activity [ Time Frame: Up to 6 years ]Will be summarized graphically and with descriptive statistics.
- Pharmacodynamic markers [ Time Frame: Up to 6 years ]Two samples t-test /Wilcoxon rank sum tests will be used to compare pharmacodynamics/pharmacokinetics (PD/PK) parameters between responder and non-responders, and logistic regression analysis will also be used to evaluate the association of PD/PK parameters with response.
- Drug exposure levels [ Time Frame: Up to 6 years ]Will be summarized graphically and with descriptive statistics.
- Overall incidence and severity of all adverse events [ Time Frame: Up to 6 years ]Graded using Common Toxicity Criteria version 4.0. Safety data will be summarized using frequency and percentage, by category and severity.
- Morphologic leukemia-free state [ Time Frame: Up to 6 years ]Will be estimated along with the 95% credible interval.
- Exploratory biomarkers [ Time Frame: Up to 6 years ]Will be summarized graphically and with descriptive statistics. Peripheral blood and bone marrow aspirate samples will be obtained at study specified time points. Biomarker assays may include, but are not limited to, BH3 profiling and characterization of BCL-2 and related proteins, and assessment of the depth of response and monitoring of disease recurrence by assessment of minimal residual disease (MRD) in the bone marrow.
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): NCT03214562
|Contact: Courtney DiNardo, MDfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Courtney DiNardo 713-794-1141|
|Principal Investigator: Courtney DiNardo|
|Principal Investigator:||Courtney DiNardo||M.D. Anderson Cancer Center|