PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
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|ClinicalTrials.gov Identifier: NCT04022785|
Recruitment Status : Recruiting
First Posted : July 17, 2019
Last Update Posted : October 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Myelodysplastic Syndrome Myelodysplastic/Myeloproliferative Neoplasm Myeloproliferative Neoplasm||Drug: Azacitidine Drug: BRD4 Inhibitor PLX51107||Phase 1|
I. To determine the minimum safe and biologically-effective dose of the combination of PLX51107 and azacitidine (AZA).
I. To determine overall response rate (ORR) rate including CR (complete remission) + CRp (complete remission with incomplete platelet recovery) + CRi (complete remission with incomplete count recovery) + CRh (complete remission with partial hematologic recovery), partial remission (PR) within 3 months of treatment initiation of PLX51107 and AZA combination in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
II. To investigate correlations of response to this combination with a pre-therapy, on-therapy, and progression 81-gene panel of gene mutations in AML.
III. To determine the duration of response (DOR), event-free survival (EFS), overall survival (OS), and number of patients bridged to stem cell transplant (SCT) and median duration to SCT from the initiation of the combination.
OUTLINE: This is a dose-escalation study of PLX51107.
Patients receive PLX51107 orally (PO) once daily (QD) on days 1-21 and azacitidine subcutaneously (SC) or intravenously (IV) over 15 minutes on days 8-14 and 22-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, then every 6-12 months for 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||32 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of PLX51107 (A Novel Bromodomain Inhibitor) in Combination With Azacytidine for Patients With Myelodysplastic Syndrome and Acute Myeloid Leukemia (AML)|
|Actual Study Start Date :||September 9, 2019|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Treatment (BRD4 Inhibitor PLX51107, azacitidine)
Patients receive PLX51107 PO QD on days 1-21 and azacitidine SC or IV over 15 minutes on days 8-14 and 22-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Given IV or SC
Drug: BRD4 Inhibitor PLX51107
- Incidence of adverse events [ Time Frame: Up to 5 years ]Toxicity type and severity will be summarized for each patient cohort using frequency tables. Per-treated analysis will be performed to include any patient who received the treatment regardless of the eligibility nor the duration or dose of the treatment received.
- Minimum safe and biologically effective dose [ Time Frame: Up to 28 days ]The minimum safe and biologically-effective dose is the highest dose level in which < 2 patients of 6 develop first cycle dose limiting toxicity.
- Overall response rate [ Time Frame: Within 3 months of treatment initiation ]Will be defined as blast count reduction, hematologic improvement, partial remission, complete remission (CR), complete remission with incomplete count recovery, complete remission with incomplete platelet recovery, complete remission with partial hematologic recovery. Will be calculated and credible interval will be provided. Wilcoxon rank sum test or Fisher's exact test will be used to evaluate the association between patient prognostic factor (e.g. lab result and gene mutation) and response.
- Gene mutations in acute myeloid leukemia [ Time Frame: Up to 5 years ]Pre-therapy, on-therapy, and progression 81-gene panel of gene mutations will be correlated with response.
- Duration of response [ Time Frame: Number of days from the date of initial response to the date of first documented disease progression/relapse or death, whichever occurs first, assessed up to 5 years ]Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
- Event-free survival [ Time Frame: Number of days from the date of treatment initiation to the date of documented treatment failure, relapses from CR, or death from any cause, whichever occurs first, assessed up to 5 years ]Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
- Overall survival [ Time Frame: Time from treatment start until death or last follow up, assessed up to 5 years ]Will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
- Number of patients bridged to stem cell transplant (SCT) [ Time Frame: Up to 5 years ]
- Median duration to SCT from initiation of combination [ Time Frame: Up to 5 years ]
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): NCT04022785
|Contact: Naveen Pemmarajufirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Naveen Pemmaraju 713-792-4956|
|Principal Investigator: Naveen Pemmaraju|
|Principal Investigator:||Naveen Pemmaraju||M.D. Anderson Cancer Center|