Nintedanib and Azacitidine in Treating Participants With HOX Gene Overexpression Relapsed or Refractory Acute Myeloid Leukemia

Recurrent Adult Acute Myeloid Leukemia Clinical Trial

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

Status Active, not recruiting

Clinical Trial Summary

The purpose of this study is to find the appropriate dose of the study drug nintedanib when combined with azacitidine and the associated side effects of the combination in older adults with AML characterized by HOX gene overexpression who are not interested in or not considered fit for standard intensive chemotherapy. The use of the study drug nintedanib in this study is investigational. Investigational means that this medication has not yet been approved by the FDA to treat this type of cancer. Azacitidine received FDA Approval in 2004 for myelodysplastic syndrome (a blood cancer related to AML) and has a National Comprehensive Cancer Network (NCCN) guideline recommendation for treatment of older adults who are not candidates for or decline intensive remission induction therapy. We expect participation to continue in this study based on each participant's response to the drug, and ability to tolerate treatment. Participants may continue to receive study treatments for 6 cycles (one cycle is 28 days long). If the 6 cycles of treatment is completed, participants may be moved on to a maintenance phase of treatment. Treatment will continue until the participant's leukemia gets worse, or they experience serious side effects, have a break in treatment for more than 56 days or the study doctor feels it is best for study treatments to stop.

Clinical Trial Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

EXPLORATORY OBJECTIVES:

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. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A
• Fibroblast Growth Factor Basic Form Measurement
• FLT3 Internal Tandem Duplication
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Recurrent Adult Acute Myeloid Leukemia
• Refractory Acute Myeloid Leukemia

• NCT number: NCT03513484
• Study type: Interventional
• Source: Northwestern University
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 14, 2018
• Completion date: January 2027