Nintedanib and Azacitidine in Treating Participants With HOX Gene Overexpression Relapsed or Refractory Acute Myeloid Leukemia
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|ClinicalTrials.gov Identifier: NCT03513484|
Recruitment Status : Recruiting
First Posted : May 1, 2018
Last Update Posted : December 4, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A Fibroblast Growth Factor Basic Form Measurement FLT3 Internal Tandem Duplication Recurrent Adult Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia||Drug: Azacitidine Other: Laboratory Biomarker Analysis Drug: Nintedanib||Phase 1|
I. To identify maximum tolerated dose (MTD) of nintedanib for combination treatment of nintedanib and azacytidine (5-azacitidine) in the treatment of newly diagnosed and relapsed/refractory acute myeloid leukemia with HOX overexpression and who are ineligible for intensive chemotherapy.
I. Adverse events (AEs) including dose limiting toxicities (DLTs) will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 4.03.
II. To determine median overall survival. III. To determine complete remission (CR) rate.
I. To determine composite CR rate (CR + complete remission with incomplete platelet recovery [CRp] + complete remission with incomplete hematological recovery [Cri]).
II. To determine duration of confirmed response. III. To determine event free survival. IV. To determine leukemia free survival. V. To establish correlation between response and pre-treatment Fgf2 levels and change in Fgf-2 levels during treatment.
OUTLINE: This is a dose-escalation study of azacitidine.
Participants receive nintedanib orally (PO) twice daily (BID) on days 1-28 and azacitidine intravenously (IV) or subcutaneously (SC) on days 1-7. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, participants may discontinue treatment, receive nintedanib every 4-8 weeks, or receive nintedanib and azacitidine every 4-8 weeks.
After completion of study treatment, participants are followed up at every 3 months for 12 months and then every 6 months for up to 24 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||44 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib, Open Label, Combination Study of Nintedanib With 5-Azacitidine in Acute Myeloid Leukemia Characterized by HOX Gene Overexpression, That Are Not Candidates of Intensive Chemotherapy|
|Actual Study Start Date :||November 14, 2018|
|Estimated Primary Completion Date :||March 1, 2020|
|Estimated Study Completion Date :||January 2021|
Experimental: Treatment (nintedanib, azacitidine)
Participants receive nintedanib PO BID on days 1-28 and azacitidine IV or SC on days 1-7. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of 6 courses, participants may discontinue treatment, receive nintedanib every 4-8 weeks, or receive nintedanib and azacitidine every 4-8 weeks.
Given IV or SC
Other: Laboratory Biomarker Analysis
- Maximum tolerated dose (MTD) [ Time Frame: Up to 28 days ]Will be defined as the highest dose that causes dose limiting toxicities (DLTs) in < 2 of 6 patients.
- Incidence of adverse events [ Time Frame: Up to 24 months ]Adverse event assessments and laboratory tests will be performed at baseline, and continuously throughout the study at the beginning of each subsequent cycle.
- Overall survival [ Time Frame: Up to 24 months ]Will be summarized using Kaplan-Meier curves. Median overall survival with 95% confidence interval will be calculated.
- Complete remission (CR) rate [ Time Frame: Up to 24 months ]
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): NCT03513484
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|Contact: Jessica K. Altman 312-695-6180 email@example.com|
|Principal Investigator: Jessica K. Altman|
|Principal Investigator:||Jessica Altman||Northwestern University|